MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

DOHLEDAT

The ‘super five’ for concussion treatment supplements

DHA, pro-resolving mediators, magnesium L-threonate, glutathione and curcumin.

ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller “Inside-Out Health,” and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science degree in human nutrition. The ACA Sports Council named him “Sports Chiropractor of the Year” in 2015. He is on the advisory board for the Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A frequently published author in peer-reviewed journals and other mainstream publications, he is a thought leader in his field and practice. His new book, “Superhighway to Health,” was published in June 2021. He can be reached at drrobertsilverman.com.

Flavonoid 7,8-dihydroxyflavone

  • Potent and selective small molecule tyrosine kinase receptor B agonist
  • Can mimic the effects of brain-derived neurotrophic factor

SOD1(G93A) mice

Animal model

Found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves

  • Found to act as a potent and selective small-molecule agonist of the tropomyosin receptor kinase B (TrkB)
    • Main signaling receptor of the neurotrophin brain-derived neurotrophic factor (BDNF)
  • Orally bioavailable
  • Able to penetrate the blood–brain barrier
  • Prodrug of 7,8-DHF with greatly improved potency and pharmacokinetics, R13 ( formerly, R7)
    • Under development for the treatment of Alzheimer's disease

Animal models of a variety of central nervous system disorders

  • Therapeutic efficacy in:
    • Depression,
    • Alzheimer's disease
    • Cognitive deficits in schizophrenia
    • Parkinson's disease
    • Huntington's disease
    • Amyotrophic lateral sclerosis
    • Traumatic brain injury,
    • Cerebral ischemia,
    • Fragile X syndrome,
    • Rett syndrome
  • en.wikipedia.org/wiki/Tropoflavin

Animal models of age-associated cognitive impairment

  • 7,8-DHF also shows efficacy
  • Enhances memory consolidation and emotional learning in healthy rodents
  • Powerful antioxidant activity independent of its actions on the TrkB receptor
  • Protects against
    • Glutamate-induced excitotoxicity
    • 6-hydroxydopamine-induced dopaminergic neurotoxicity
    • Oxidative stress-induced genotoxicity
  • Found to block methamphetamine-induced dopaminergic neurotoxicity
  • 7,8-DHF and various other reported small-molecule TrkB agonists
    • Might be mediating their observed effects by other means
  • 7,8-DHF has been found to act as a weak aromatase inhibitor in vitro (Ki = 10 mcM)
    • This might not be the case in vivo
  • Inhibit aldehyde dehydrogenase and estrogen sulfotransferase in vitro
    • Not yet been confirmed in vivo
  • Does not show any inhibitory activity on 17ß-hydroxysteroid dehydrogenase
    • In vitro antiestrogenic effects at very high concentrations
  • 7,8-DHF act as TrkB agonists in vitro
  • Antagonist of TrkB in vitro appears to be:
    • Diosmetin (5,7,3'-trihydroxy-4'-methoxyflavone)
    • Norwogonin (5,7,8-trihydroxyflavone)
    • 4'-dimethylamino-7,8-dihydroxyflavone (4'-DMA-7,8-DHF, eutropoflavin),
    • 7,8,3'-trihydroxyflavone,
    • 7,3'-dihydroxyflavone,
    • 7,8,2'-trihydroxyflavone,
    • 3,7,8,2'-tetrahydroxyflavone,
    • 3,7-dihydroxyflavone.
    • Highly hydroxylated analogue gossypetin (3,5,7,8,3',4'-hexahydroxyflavone)
  • en.wikipedia.org/wiki/Tropoflavin

Myši

  • "7,8-Dihydroxyflavone Rescues Lead-Induced Impairment of Vesicular Release: A Novel Therapeutic Approach for Lead Intoxicated Children"
  • Pb2+-induced impairment of calcium influx in Schaffer collateral-CA1 synaptic terminals.
    • Intraperitoneal injections of Pb2+ rats with the TrkB receptor agonist 7,8-dihydroxyflavone (5 mg/kg) for 14-15 days
      • Reversed all Pb2+-induced impairments of presynaptic transmitter release at Schaffer collateral-CA1 synapses
    • Pharmacological activation of TrkB receptors by small molecules such as 7,8-dihydroxyflavone
      • Can reverse long-term effects of chronic Pb2+ exposure on presynaptic terminals,
        • TrkB receptor activation as a promising therapeutic intervention in Pb2+-intoxicated children.
  • academic.oup.com/toxsci/article/161/1/186/4344844

Zvířata

  • Shown to have no toxic effects
  • Have neuroprotective properties in preclinical studies (Jang et al., 2010; Zhang et al., 2014)
  • Proposed as a pro-neurotrophic treatment for neurodevelopment disorders (Du and Hill, 2015).
  • academic.oup.com/toxsci/article/161/1/186/4344844

In vitro

  • O-Methylated Metabolite of 7,8-Dihydroxyflavone
  • Activates TrkB Receptor and Displays Antidepressant Activity
  • Blocking methylation, using COMT inhibitors
    • Diminishes the agonistic effect of TrkB activation by 7,8-DHF or 4'-dimethylamino-7,8-DHF
  • O-methylated metabolites are implicated in TrkB receptor activation in the brain.
  • COMT is involved in the inactivation of the catecholamine neurotransmitters.
  • Enzyme transfers a methyl group to the catecholamine from the methyl donor, S-adenosyl methionine
  • Compounds with a catechol structure, like
    • Catechol estrogens
    • Catechol-containing flavonoids - are substrates of COMT.
  • www.karger.com/Article/FullText/346920

Bacopa monnieri and polygala tenuifolia

P.O. suplementace 7,8-DHF lidem

  • Estimates being mathematically approximated from rodent research.
  • The majority of rodent research does use intravenous injections however, with limited studies using oral ingestion
  • Oral ingestion does appear to have effects, with rat studies noting:
    • 5mg/kg being effective in the cognitively unwell mouse (chronic usage)
    • 10mg/kg being effective in the cognitively well rat (subchronic use)
    • 30mg/kg in the mouse being acutely effective
  • Approximately 1mg/kg for subchronic or chronic usage in humans
    • Acute dose correlating to approximately 2.5mg/kg
  • 7,8-DHF activates the Nrf2 antioxidant response protein
    • Via upstream activation of PI3K/Akt signaling
      • Via activation of TrkB in some models
  • 7,7-DHF also activates PI3K/Akt via TrkB-independent mechanisms.
  • 7,8-DHF is orally bioavailable in mice
  • Subject to significant first-pass metabolism

Myši

  • Peripheral injections of 7,8-DHF (5mg/kg) to the mouse
    • Can activate TrkB in the brain, suggesting that it can cross the blood-brain barrier

In vitro

  • When 7,8-DHF appears in the blood, it can pass the blood-brain barrier and reach the brain to exert its effects.
  • 7,8-DHF has been noted to have an inhibitory action on estrogen sulfotransferase in vitro
    • Slightly weaker potency than some other tested flavonoids
  • 7,8-DHF has inhibitory action on aldehyde dehydrogenase 2

Krysy

  • Neurotoxicity induced by methamphetamine
    • Reduced with an acute oral preload of 7,8-DHF (30mg/kg in the mouse )
    • 10mg/kg being effective in subchronic methamphetamine exposure
    • Associated with less dopamine transporter reduction and fewer behavioural abnormalities
  • Can have a potential antiaddictive effect in response to cocaine treatment in the rat
    • Mimicked with 7,8-DHF injections.

Myši

  • Intraperitoneal administration of 7,8-DHF to an animal model of amyotrophic lateral sclerosis (ALS)
    • Appears to confer motor benefits
      • Related to a preservation of dendritic spines of spinal neurons
    • Increase in neuromuscular transmission has been noted with 7,8-DHF incubation (10 mcM) in diaphragm muscles of the mouse
      • May be relevant to ALS
  • 7,8-DHF may have therapeutic potential for ALS, although no human studies have been performed to date.
  • examine.com/supplements/7-8-dihydroxyflavone/research/#sources-and-composition

Monkey

  • Previous reports showed that 7, 8- dihydroxyflavone (7, 8-DHF) as a potent TrkB agonist can mimic BDNF and play neuroprotective roles for mouse dopaminergic neurons.
  • Safety and neuroprotective effects are unclear in monkey models of PD.
  • 7, 8-DHF could be absorbed and metabolized into 7-hydroxy-8-methoxyflavone through oral administration in monkeys.
  • Half-life time of 7, 8-DHF in monkey plasma is about 4–8 hrs
  • Monkeys maintain health state throughout the course of seven-month treatments of 7, 8-DHF (30 mg/kg/day)
  • 7, 8-DHF treatments can prevent the progressive degeneration of midbrain dopaminergic neurons
    • Attenuating neurotoxic effects of MPP+
    • Strong neuroprotective effects in monkeys
  • May be transited into a clinical useful pharmacological agent.
  • www.nature.com/articles/srep34339

Mice with ALS (SOD1G93A)

  • 5 mg/kg of flavonoid 7,8-dihydroxyflavone
  • Plants
    • Godmania aesculifolia
    • Tridax procumbens
  • Up to 105 days caused a significant improvement in motor deficits.
  • Ability to cross the blood-brain barrier
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC7707995/
  • 7,8-dihydroxyflavone (7,8-DHF) has neuroprotective and regulatory properties on neuromuscular transmission (Mantilla and Ermilov, 2012)

Mouse

Transgenic ALS mouse model

  • Chronic administration of 7,8-DHF significantly improved motor deficits and enhanced lower neuronal survival in the (Korkmaz et al., 2014)
  • Neuroprotective and regulatory properties on neuromuscular transmission (Mantilla and Ermilov, 2012)
  • www.frontiersin.org/articles/10.3389/fphys.2020.00063/full

AAP70-1


Anemarrhena asphodeloides Bunge is known as “Zhi-mu” in traditional Chinese medicine. The pure compound and its crude extract show obvious neuroprotective activities. Anemarrhena asphodeloides polysaccharides (AAPs) are the main bioactive components isolated from A. asphodeloides. Zhang et al. (2020) isolated and purified a new polysaccharide named AAP70-1 from the AAPs. AAP70-1 is a homogeneous polysaccharide composed of glucose and fructose. Pretreatment with APP70-1 protects SH-SY5Y cells from CoCl2-induced apoptosis. The low molecular weight and small branching structure of AAP70-1, as well as the presence of fructose, may be linked to its neuroprotective effects. The data suggest that AAP70-1 has a neuroprotective potential, to some extent, but whether it can prevent or treat NDDs requires more data.
  • Neural Regeneration Research 17(9):p 1907-1912, September 2022. | DOI: 10.4103/1673-5374.335142

Acelty L karnitine

24 male adult Sprague-Dawley rats

  • Randomly divided into 4 groups
  • Laminectomy at T9-T11 in all of the rats
  • Normal saline or acetyl L-carnitine (300 mg/kg) was injected
  • SCI was done by 30 gr compression
  • After 4 weeks, spinal cords were extracted for morphometry and immunohistochemistry study
  • Motoneurons reduced after SCI
  • Acetyl L-carnitine reduced this reduction in addition to reduction of astrocytes (p<0.05).
  • In gliosis reaction, acetyl L-carnitine could
    • Reduce astrocytes
    • Increase oligodendrocytes (about 3 times)
    • Improvement may be due to myelin production
    • Also due to better conduction
  • Sadra Jamshidi Marjan Heshmati Mohammadreza Jalali Nadoushan

Acetylcholin

  • Sirtuiny
    • Prodlužují délku života
    • Odštěpují acetát, na acetylcholin
  • „superagers“ mají vysokou mentální schopnost až do vysokého věku
    • Mají vysokou hladinu acetycholinu.
    • Jejich paměť je lepší a mají více neurálních spojů.
      • To tvoří výbornou paměť.
  • U většiny z nás hladina acetylcholinu klesá vlivem stárnutí, rychleji pak po 45. roce života

Acorus tatarinowii polysaccharides


Acorus tatarinowii Schott is a common traditional Chinese medicine for the treatment of neuropsychiatric diseases, and it has been used in the clinical practice of traditional Chinese medicine for thousands of years (Zhang et al., 2019). To investigate the bioactivity of A. tatarinowii Schott, Yan et al. (2020) extracted a crude polysaccharide named ATP50, which reduces the levels of pro-inflammatory cytokines in the brain and serum. It also improves the memory and cognitive performances of scopolamine-induced amnesiatic mice. The team isolated and purified ATP50 to produce a polysaccharide with a much lower molecular weight and a well-defined structure, called ATP50-3. The neuroprotective and anti-inflammatory effects of ATP50-3 have been studied using the BV2 microglia model induced by lipopolysaccharide (LPS) (Zhong et al., 2020). ATP50-3 has a significant anti-neuroinflammatory effect that acts by inhibiting LPS-induced over-activation of pro-inflammatory BV2 microglia and by inhibiting TLR4-mediated PI3K/Akt and MyD88/NF-?B signaling pathways that reduce the levels of inflammatory mediators and cytokines. In addition, ATP50-3 protects cortical and hippocampal primary neurons from neurotoxic damage caused by LPS-activated microglia. Thus, ATP50-3 is an effective neuroprotective agent that can inhibit neuroinflammation, and it should be assessed in preclinical trials for the treatment of NDDs.

Activating PI3K-Akt signals

Amantadine - Viregyt k

  • Dopamine agonist used for Parkinson’s disease
  • Can distribute in frontal lobes
  • Acts as an N-methyl-D-Aspartate (NMDA) receptor antagonist
  • May protect the neurons against glutamate excitotoxicity in the acute phase of TBI
  • Studies have demonstrated that amantadine in dose of 100–400 mg/d may
    • Increase the arousal
    • Improve cognitive function when given within 12 wk after the TBI
  • journals.sagepub.com/doi/full/10.1177/0963689717714102

Aminocure


Amphetamine and modafinil

H3 receptor antagonists

  • SAR110894 (3-30 mg/kg, p.o.) did not modify significantly any of the sleep/wakefulness parameters
  • SAR110068 (10 and 30 mg/kg, p.o.) myším effects for 3-4 h
    • Increased wakefulness and decreased slow wave sleep
  • Ciproxifan (10 mg/kg, i.p.) effects for 3-4 h
  • ABT-0239 (10 mg/kg, p.o.) effects for 3-4 h
  • GSK189254 (10 mg/kg, p.o.) lasted for about 1h
  • Classical psychostimulants
    • Amphetamine - dramatically higher than with the H3 compounds, and they lasted for 5 and 6 h
    • Modafinil - dramatically higher than with the H3 compounds, and they lasted for 5 and 6 h
    • But both psychostimulants produced a strong increase in theta (?) rhythm
      • Indicative of CNS side effects, such as hyperactivity or abnormal excitation
  • pubmed.ncbi.nlm.nih.gov/22561131/

Antrodia camphorata polysaccharide


Antrodia camphorata is a polyporous fungus endemic to Taiwan that is rich in polysaccharides, terpenoids, steroids, and other bioactive substances. A previous study demonstrated the anti-tumor activity of A. camphorata polysaccharide (ACP) (Popović et al., 2013). The anti-neuroinflammatory effects of ACP have recently been investigated in a mouse model of PD induced by 6-hydroxydopamine (Han et al., 2019). The ACP interventions improve the motor symptoms of mice modeling PD and greatly inhibit the expression of the NLRP3 inflammatory body and its downstream inflammatory factors. In a subsequent study, Han et al. (2020) found that ACP exhibits neuroprotective effects on a 6-hydroxydopamine-induced cell model and in an animal model of PD by inhibiting the ROS-NLRP3 signaling pathway. Thus, although the composition and structural characteristics of ACP need to be further studied, these results suggest that ACP has the potential to improve the motor symptoms of PD patients and may provide new hope for PD therapy.
  • Neural Regeneration Research 17(9):p 1907-1912, September 2022. | DOI: 10.4103/1673-5374.335142

Apios americana Medik

  • Is an herb native to North America that is widely cultivated in the USA and Japan. Its nutritious tuber is a staple food of indigenous North American people (Kim et al., 2017). Previous studies mainly reported the biological activities of A. americana Medik tuber extracts (Sohn et al., 2015; Kaneta et al., 2016). Apios americana Medik flower polysaccharide (AFP-2), a purified polysaccharide, was extracted from flowers of A. americana Medik to investigate its beneficial effects on health (Chu et al., 2019). In vitro experiments showed that AFP-2 activates the intracellular antioxidant system through the Sirtl/Nrf2 signaling pathway, and it effectively reduces the accumulation of ROS and mitochondrial dysfunction caused by H2O2. At the molecular level, autophagy was found to be involved in the antioxidant process of AFP-2 in H2O2-induced PC12 cells. Further studies showed that AFP-2 activates autophagy by inhibiting the phosphorylation of the Akt-mTOR pathway. In conclusion, AFP-2 is an effective antioxidant with potential neuroprotective effects that may be applied to treat NDDs.

Astragalus

  • Kořen drcený nebo extrakty
  • Stimuluje novotvorbu cév a to je pro hojení moc důležité

BDNF (brain derived neurotropic factor) elevace


Boswellia — Boswellia (Boswellia serrata)

  • Herbal extract
  • Beneficial for concussion patients with diffuse axonal injury (DAI)
    • A type of traumatic brain injury resulting from a blunt injury to the head
  • Boswellia has been shown to encourage neurorecovery by enhancing cognitive function
ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller “Inside-Out Health,” and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science degree in human nutrition. The ACA Sports Council named him “Sports Chiropractor of the Year” in 2015. He is on the advisory board for the Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A frequently published author in peer-reviewed journals and other mainstream publications, he is a thought leader in his field and practice. His new book, “Superhighway to Health,” was published in June 2021. He can be reached at drrobertsilverman.com.

Branched-chain amino acids


Bromkriptin mesylate


Butyrát

  • Při tendenci ke spasticitě nebo ke křečím
  • Butyrát jako ochrana před glutamátovou excitotoxcitou
  • Zlepšuje soustředění a neuroplasticitu

CBD kapky z konopí

  • Působí neuroprotektivně

CSF1R inhibitor, Plexxikon (PLX) 5622

  • Microglia, the primary innate immune cells in brain
    • Dependent on colony stimulating factor 1 receptor (CSF1R) signaling for their survival

Preclinical study

  • Delayed depletion of chronically activated microglia on functional recovery and neurodegeneration up to 3 months postinjury
  • Plexxikon (PLX) 5622 to adult male C57BL/6J mice at 1 month after controlled cortical impact
    • To remove chronically activated microglia
    • Inhibitor was withdrawn 1-week later to allow for microglial repopulation
  • Following TBI
    • Repopulated microglia displayed a ramified morphology similar to that of Sham uninjured mice
    • Microglia in vehicle-treated TBI mice showed the typical chronic posttraumatic hypertrophic morphology
  • PLX5622 treatment limited TBI-associated neuropathological changes at 3 months postinjury
    • Smaller cortical lesion,
    • Reduced hippocampal neuron cell death
    • Decreased NOX2- and NLRP3 inflammasome-associated neuroinflammation
    • Delayed depletion of chronically activated microglia after TBI led to
      • Widespread changes in the cortical transcriptome
      • Altered gene pathways involved in neuroinflammation, oxidative stress, and neuroplasticity
  • PLX5622-treated TBI mice
    • Improved long-term motor and cognitive function recovery through 3 months postinjury
  • Chronic phase removal of neurotoxic microglia after TBI using CSF1R inhibitors
    • Markedly reduce chronic neuroinflammation and associated neurodegeneration
      • As well as related motor and cognitive deficits.
  • www.jneurosci.org/content/40/14/2960

CSF1R small-molecule inhibitors

  • Enabled selective elimination of microglia under both physiological (Elmore et al., 2014) and pathological conditions (Szalay et al., 2016; Jin et al., 2017; Li et al., 2017)
  • Oral administration of CSF1R inhibitors
    • Rapidly deplete >95% of all microglia in the CNS within 7 d of treatment (Elmore et al., 2014)

Plexxikon (PLX)

  • Chronic and evolving microglial activation is detrimental following severe TBI (Byrnes et al., 2012; Loane et al., 2014; Pischiutta et al., 2018),
  • Prolonged inhibition of microglia is unlikely to be therapeutic
    • Microglia perform critical functions such as
      • Synaptic pruning and restoration of tissue homeostasis after pathological insult (Salter and Stevens, 2017)
  • Withdrawal of CSF1R inhibitors in microglia-depleted mice
    • Results in rapid self-renewal and repopulation of microglia in the CNS (Elmore et al., 2014, 2015)
    • Can improve cognitive function recovery in hippocampal lesion studies (Rice et al., 2017)
  • Removing neurotoxic microglia by short-term treatment with CSF1R inhibitors may have a long-term effect on the lesion microenvironment and disrupt the chronic trajectory of neurodegeneration.
  • www.jneurosci.org/content/40/14/2960

Mouse hippocampal lesion model

  • Depletion of microglia by a 30 d treatment with a CSF1R inhibitor, Plexxikon (PLX) 3397
  • Improved cognitive recovery and reduced proinflammatory gene expression in the injured hippocampus (Rice et al., 2015)
  • www.jneurosci.org/content/40/14/2960

CSPGs/PTPsigma interactions

Canagliflozin

  • ‘dual inhibitor of SGLT2 and AChE’
  • Inhibition constant Ki (i.e., the concentration required to produce half-maximum inhibition) against AChE was 0.12859 µM
  • Patients taking canagliflozin reach a serum drug concentration of 10µM, and the brain/serum ratio of canagliflozin is 0.3
  • Amount of canagliflozin penetrating the brain (3 µM) is enough to inhibit AChE
  • Greatest potential of inhibiting AChE
  • May be a preferable solution in patients with T2DM who would also benefit from the inhibition of acetylcholinesterase.

Cannabinoids


Carvacol

  • Suppression of Transient Receptor Potential Melastatin 7
    • By Carvacrol
    • Protects against Injured Spinal Cord
      • By Inhibiting Blood-Spinal Cord Barrier Disruption
  • Blood-spinal cord barrier (BSCB) disrupted after a spinal cord injury (SCI)
    • Inflammation and apoptotic cell death of neurons and oligodendrocytes
    • Permanent neurological deficits
  • Transient receptor potential melastatin 7 (TRPM7)
    • Involved in the pathological processes in many neuronal disease
      • Traumatic brain injury,
      • Amyotrophic lateral sclerosis,
      • Parkinsonism dementia,
      • Alzheimer's disease
  • Carvacrol (CAR), a TRPM7 inhibitor
    • Protect reducing oxidative stress
    • Inhibiting the endothelial nitric oxide synthase pathway
    • calcium-mediated non-selective divalent cation channel
      • Critical role after SCI in rats

Rats were contused at T9

  • CAR (50 mg/kg) intraperitoneally immediately and 12 h after SCI
  • Same dose once a day for 7 days
  • TRPM7 was found to be up-regulated after SCI in both in vitro and in vivo studies
    • Expressed in blood vessels alongside neurons and oligodendrocytes
  • CAR treatment suppressed BSCB disruption
    • By inhibiting the loss of tight junction (TJ) proteins
    • Preserved TJ integrity
  • CAR also reduced apoptotic cell death
    • Improved functional recovery after SCI
      • By preventing BSCB disruption caused by blood infiltration and inflammatory responses
  • Blocking the TRPM7 channel
    • Can inhibit the destruction of the BSCB
    • Potential target in therapeutic drug development for use in SCI.
  • DOI: 10.1089/neu.2021.0338

Cerebrolysin

  • Lyzát mozkové tkáně pro obnovu poškozeného CNS

Cis antibody

  • Spot only the toxic cis P-tau
    • Neutralize its toxicity to neurons

Treating TBI mice with cis antibody

  • Can stop brain damage after TBI
  • Prevent its debilitating long-term consequence of Alzheimer’s and CTE
  • Cis P-tau is an early driver of TBI
  • Its related Alzheimer’s disease and CTE
    • Can be effectively blocked by antibody therapy.
  • It is critically important to allow the body defense system to remove the toxic tau protein completely before another concussion occurs
  • www.wbur.org/news/2015/07/15/brain-injury-alzheimers-research

Citicoline

Citicoline and Omega-3 Fatty Acid Effects in Veterans With Traumatic Brain Injury (TBI) 2013-2017

  • Studie, ale nedodělaná
  • 28-day administration period.
    • Citicoline - má zajímavé popisy stran neuroregenerace
    • Omega-3 2000 mg daily Omegabrite - tohle samo o sobě asi také
    • Rice bran oil daily in 500 mg doses - tento olej stimuluje novotvorbu cév a mohl by být také hojivý
    • Microcrystalline Cellulose in 470 mg doses - vláknina do střeva není špatně - otázka je jaký poměr k. propionové /butyrátu to dá
  • Dá se dohledat, proč byla zrušena a jaké měla výsledky ?
  • clinicaltrials.gov/ct2/show/NCT01515917?type=Intr&cond=Brain+Injuries%2C+Traumatic&draw=7&rank=544

Clenbuterol

  • Působil muskuloprotektivně i neuroprotektivně u ALS

Coenzym Q10

  • Určitě neuškodí

Creatine

  • Compound found naturally in the body
  • Promote neurogenesis and neuroplasticity.

DJ001

  • Highly specific
  • Selective and non-competitive protein tyrosine phosphatase-sigma (PTPsigma) inhibitor
  • IC50 of 1.43 mcM
  • no inhibitory activity against other phosphatases
    • Only modest inhibitory activity against Protein Phosphatase 5
  • DJ001 promotes promote hematopoietic stem cell regeneration

In Vitro

  • 5-1000 ng/mL; 3-7 days; BM KSL cells treatment
  • Increases the percentages and numbers of BM KSL cells in culture
  • Increases the numbers of colony forming cells (CFCs) in 3 day culture of BM KSL cells
  • BM KSL cells are irradiated with 300 cGy and placed in media (containing 20 ng/mL Thrombopoietin, 100 ng/mL stem cell factor (SCF), 50 ng/mL Flt3 ligand, TSF) with and without 1 mcg/mL DJ001 for 3 days
    • DJ001 treatment increases recovery of BM CFCs and multipotent colony-forming unit–granulocyte erythroid monocyte megakaryocyte (CFU-GEMM) colonies compared with control cultures[1].
  • Concentration: 5 ng/mL, 10 ng/mL, 100 ng/mL, 1000 ng/mL
  • Incubation Time: 3 days or 7 days
  • Result:
    • Increased the percentages and numbers of BM KSL cells.
    • Increased the numbers of colony forming cells (CFCs) in 3 day culture of BM KSL cells.

In Vivo

  • 5 mg/kg; subcutaneous injection; for 24 hours; female C57BL/6 mice
    • Significantly decreases the percentage of apoptotic BM KSL cells in C57BL/6 mice at 24 h following 500 cGy TBI
  • Suppresses radiation-induced HSC apoptosis via activation of the RhoGTPase, RAC1, and induction of BCL-XL
  • www.medchemexpress.com/dj001.html

Decorin

In vitro


Deletion of four PNN components - brevican, neurocan, tenascin-C and tenascin-R

Quadruple knockout mouse


Dictyophora echinovolvata

  • Edible fungus
  • Grown and consumed in China for more than a thousand years
  • Anti-tumor, anti-proliferation, anti-oxidation, and other
  • Yu et al. (2017) investigated the neuroprotective effects of Dictyophora echinovolvata polysaccharide (DEVP)
  • DEVP greatly inhibits H2O2-induced cellular neurotoxicity
  • Reverses H2O2-induced cell morphological changes and intracellular ROS aggregation
  • Altered expression levels of Bax, cleaved caspase-3, cytochrome C, and Bcl-2 proteins further
    • Neuroprotective effects of DEVP through the inhibition of the mitochondrial apoptotic pathway.
  • DEVP may be a potential candidate that prevents NDDs by combating oxidative stress and apoptosis.

Disepavit

.disepavit.jpg

Donepezil

Multicenter Evaluation of Memory Remediation After TBI With Donepezil (MEMRI-TBI-D)

  • Evaluate the effects of treatment with donepezil on verbal memory after TBI

Epidermal growth factor receptor (EGFR) pathways inhibition

  • CSPGs also activate epidermal growth factor receptor (EGFR) pathways
  • Suppressing the kinase activity of EGFR, or its downstream mitogen-activated protein kinase (MAPK)
    • Reverses inhibition of axon growth by CSPGs (Koprivica et al., 2005; Kaneko et al., 2007)
  • Inhibition of ErbB1, an EGFR, by either pharmacological or genetic approach
    • Promotes neuronal growth in the presence of CSPG, CNS myelin, or fibrinogen (Leinster et al., 2013).
  • www.frontiersin.org/articles/10.3389/fncel.2020.00174/full

Estrogeny

Lanzeto

  • Bioidentické estrogeny ve spreji - do oblasti hlavy a krku
  • K tomu tbl. progesteronu
    • Dle patentu o neuroregeneraci to nemůže být kde jaký progesteron...
      • Medroxyprogesterone acetate (MPA) = ŠPATNÝ !!!

Nestorone® 5 mg/day or less

  • Neurodegeneration is prevented or reduced
  • From 100 to 450 mcg/day by the patient
  • Interrupted dosage
    • 3 weeks on the dosage followed by 1 week off the dosage.
  • Can be transdermal form

Estradiol 10 - 150 mcg/day

  • Absorbed by the patient
  • Simultaneously treating a female

Progestin compound preferred embodiment

  • Nestorone® 100 - 450 mcg/day absorbed by the patient
  • 18-methyl Nestorone®
  • Nomegestrol acetate 2.5 - 5 mg/day
  • Trimegestone 0.5 - 1 mg/day
  • Norgestimate
  • Dienogest 2 -3 mg/day
  • Drospirenone 3 mg/day
  • Chlormadinone acetate 5 mg/day
  • Promegestone
  • Retroprogesterone
    • 17-hydroxyprogesterone
  • Progestin compound to reduce the ischemic lesions in the subcortical structures
    • May reduce an infarct zone after a stroke within a period of about 6 hours of that event
  • Moderate traumatic brain injury
    • Administration of therapeutic levels reduce the area of brain damage
    • Nestorone® - 0.03 - 1.0 mg/day
    • Preferably 100 - 800 mcg/day
      • Irrespective of the dosages taken orally or otherwise

Progesterone

  • Efficient at a dose of 8 mg/Kg
    • 100-times lower dose of Nestorone® (0.08 mg/Kg) showed similar neuroprotective efficacy

Segesterone acetate - Nestorone®/Estradiol

Systemic application of the Extracellular LAR Peptide (ELP) or Intracellular LAR Peptide (ILP)

Caudal spinal cord in ELP/ILP-treated mice

  • Increased the density of serotonergic axons in the spinal cord 5-7 mm caudal to dorsal over-hemitransection T7 (Fisher et al., 2011).
  • Longitudinal sections containing the lesion demonstrate
    • Regrowth of many 5-HT-positive axons into the CSPG-rich scar tissues
  • Peptide treated mice also performed
    • Better behavioral recovery, including
      • Enhanced locomotor Basso Mouse Scale scores
      • Reduced grid walk errors of the hind paws a few weeks after injury
  • LAR blockade a pharmacological approach improves axonal growth and behavioral recovery in adult rodents with SCI
    • Great therapeutic potential for CNS injuries
  • austinpublishinggroup.com/neurological-disorders-epilepsy/fulltext/ajnde-v2-id1010.php

Fluoxetine

  • Promote TRKB phosphorylation
  • Reopen critical period-like plasticity in the adult brain
  • Disrupts the interaction between TRKB and PTPsigma by binding to the transmembrane domain of TRKB
  • ChABC and fluoxetine reopen critical period-like plasticity in the adult visual cortex
    • By promoting TRKB signaling in PV+ neurons
      • Through inhibition of TRKB dephosphorylation by the PTPsigma-CSPG complex
  • www.jneurosci.org/content/41/5/972
  • Plasticity
    • Ability of the brain to change itself through establishing new neuronal connections and rewiring existing ones
    • Prominent in early life and it peaks during so-called “critical periods” when the ability of the brain to adapt is at its highest (Wiesel, 1982).
  • After the end of the critical period, plasticity persists but at significantly diminished levels (Hübener and Bonhoeffer, 2014).
  • Closure of the critical periods is mediated by changes in cortical excitatory/inhibitory (E/I) balance
    • Take place because of maturation of cortical inhibitory interneurons.
  • www.jneurosci.org/content/41/5/972
  • Antidepressants activate neurotrophic receptor tyrosine kinase 2 (TRKB)
    • The receptor for brain-derived neurotrophic factor (BDNF),
      • Promote plasticity through its signaling pathways (Saarelainen et al., 2003; Duman and Monteggia, 2006; Castrén and Antila, 2017; Umemori et al., 2018).

Fucoidan


Fucoidan (FPS), a sulfurated polysaccharide, is extracted from Saccharina japonica. The chemical composition of FPS is complex, and multiple fractions can be obtained during separation and purification. Various FPS fractions have broad ranges of antioxidative properties, and the differences in the sulfate/fucose content ratio determine the antioxidant activity levels (Wang et al., 2008). Several investigators have reported the neuroprotective effects of different FPS fractions both in vitro and in vivo, and they mainly function through antioxidant activities and the prevention of cell apoptosis (Wang et al., 2016). Sulfated hetero-polysaccharides (DF1s) effectively decrease lipid peroxidation and increase the levels/activities of glutathione, glutathione peroxidase, malondialdehyde, and catalase in 1-methyl-4-phenyl-1,236-tetrahydropyridine mice. UF, a sulfated hetero-polysaccharide prepared from DF, protects SH-SY5Y cells from H2O catalase-induced apoptosis by regulating the PI3K/Akt signaling pathway and downstream signal transduction (Wang et al., 2017). These findings indicated that FPS and its different fractions exert great neuroprotective effects and have anti-PD potential as effective drugs for the treatment of PD.

GSK-3beta signal inibice

  • GSK-3beta signal partly mediates CSPG function
  • Its inhibitors overcome CSPG suppression of neuronal growth (Dill et al., 2008; Fisher et al., 2011)

GSK-3beta inhibitors

Lithium

  • Reported to be beneficial after CNS injuries in vivo

Lithium for treating chronic SCI patients - phase I/II clinical trials

Gabapentin

  • Reduces Reactive Gliosis and Neurodegeneration after Pilocarpine-Induced Status Epilepticus

The lithium-pilocarpine model of epilepsy in rodents

  • Neuronal network reorganization that occurs during latency (po epileptickém záchvatu / status epilepticus)
    • Determines the subsequent appearance of spontaneous recurrent seizures
  • Astrocytes - secretion of synaptogenic molecules such as thrombospondins
  • Alpha2dleta1 thrombospondin receptor antagonist gabapentin

Adult male Wistar rats

  • 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine
  • Once SE was achieved, seizures were stopped with 20 mg/kg diazepam
  • Animals then received 400 mg/kg/day gabapentin or saline for either 4 or 14 days
  • During the latency period
    • Hippocampus and pyriform cortex of SE-animals presented a profuse reactive astrogliosis
    • Increased GFAP and nestin expression
    • Gliosis intensity was dependent on the Racine stage attained by the animals
      • Peaked 15 days after SE
  • Microglia was also reactive after SE, and followed the same pattern
  • Neuronal degeneration was present in SE-animals
    • Depended on the Racine stage and the SE duration
  • Polysialic-acid NCAM (PSA-NCAM) expression was increased in hippocampal CA-1 and dentate gyrus of SE-animals
  • Gabapentin treatment was able
    • To reduce reactive gliosis
    • Decrease neuronal loss
    • Normalize PSA-NCAM staining in hippocampal CA-1

In vitro experiments

  • Dissociated mixed hippocampal cell culture exposed to glutamate
  • Subsequently treated with gabapentin or vehicle
  • Gabapentin treatment partially prevented the dendritic loss and reactive gliosis caused by glutamate excitotoxicity
  • Gabapentin treatment during the latency period after SE
    • Protects neurons
    • Normalizes PSA-NCAM
      • Probably by direct interaction with neurons and glia.

H(3)R-antagonists

Thioperamide

  • Increased W and cortical EEG fast rhythms
    • Like modafinil
    • Unlike amphetamine and caffeine
  • waking effects were not accompanied by sleep rebound

Ciproxifan

  • Increased W and cortical EEG fast rhythms
    • Like modafinil
    • Unlike amphetamine and caffeine
  • waking effects were not accompanied by sleep rebound

Imetit (H(3)R-agonist)

  • Enhanced slow wave sleep
  • Dose-dependently attenuated ciproxifan-induced W
    • Effects of both ligands involve H(3)-receptor mechanisms
  • Knockout (KO) mice confirmed:
    • Essential role of H(3)-receptors and histamine-mediated transmission in the wake properties of H(3)R-antagonists
  • Ciproxifan
    • Produced no increase in W
      • Ne cestou histidine-decarboxylase (HDC, histamine-synthesizing enzyme)
      • Ani H(1)- or H(3)-receptor KO-mice
    • Its waking effects persisted in H(2)-receptor KO-mice
      • Data validate the hypothesis that H(3)R-antagonists, through disinhibition of H(3)-autoreceptors
        • enhancing synaptic histamine
          • That in turn activates postsynaptic H(1)-receptors promoting W.
  • pubmed.ncbi.nlm.nih.gov/17288995/


HB-GAM (pleiotrophin)

  • Reverses inhibition of neural regeneration by the CNS extracellular matrix
  • HB-GAM - heparin-binding growth-associated molecule - pleiotrophin
    • A CS-binding protein
    • Expressed at high levels in the developing CNS
    • Reverses the role of the CS chains in neurite growth of CNS neurons in vitro
      • From inhibition to activation
  • CS-bound HB-GAM
    • Promotes neurite growth
    • Through binding to the cell surface proteoglycan glypican-2
  • HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPsigma (protein tyrosine phosphatase sigma)
  • Strongly downregulated in the adult brain
  • hal-amu.archives-ouvertes.fr/hal-01468727

In vitro studies

  • HB-GAM increases
    • Dendrite regeneration in the adult cerebral cortex
    • Axonal regeneration in the adult spinal cord
  • HB-GAM/pleiotrophin
    • Initially isolated as a heparin-binding neurite outgrowth-promoting factor for central neurons
  • Its expression peaks during the first 3–4 weeks of postnatal development in rat brain
    • Heightened plasticity of the juvenile brain
    • Expression level up to 10–15 ug/g of wet tissue weight
      • Might be sufficient to modulate matrix structures that typically inhibit neural plasticity and regeneration
  • HB-GAM is secreted from neurons and glial cells
    • Upon cleavage of a classic-type secretion signal
    • Binds CS side chains of CSPGs with nanomolar Kd values
    • Lines nearly all fiber tracts of the early postnatal rat brain
  • Growth factor Midkine
    • Displays homology with HB-GAM
    • Was recently reported to partially overcome CSPG inhibition of neurite extension
  • HB-GAM as a candidate molecule
    • To modify interactions of CNS neurons with inhibitory ECM structures such as CSPGs

Glypican-2 of the neuron surface

  • Is required for HB-GAM-induced neurite outgrowth on CSPG substrate
  • Downregulation of glypican-2 expression in CNS neurons
    • Clearly inhibited the neurite outgrowth-promoting effect of HB-GAM on aggrecan
  • Glypican-2 located on the neuron surface is required to mediate neurite outgrowth on aggrecan in the presence of HB-GAM.
  • Glypican-2 as a neurite outgrowth receptor in mammals
  • Glypican-2 is highly expressed in mammalian central neurons that extend neurites
  • Glypicans regulate signaling of Wnts, Hedgehogs, fibroblast growth factors and bone morphogenetic proteins
  • hal-amu.archives-ouvertes.fr/hal-01468727

Heparan sulfate surface

  • Neurite outgrowth induced by HB-GAM
    • Depend on binding to heparan sulfate (HS) chains of the neuron surface

Heparinase III

  • The heparinase that cleaves preferentially HS instead of highly sulfated heparin-type chains
  • Caused a nearly complete inhibition of neurite outgrowth on aggrecan in the presence of HB-GAM

Heparinases I and II

  • Had little or no effect on neurite outgrowth

HS proteoglycan syndecan-3 (N-syndecan)

  • HB-GAM receptor
  • Syndecan-3 knockout neurons
    • No difference was observed in neurite outgrowth

Phospholipase C

HB-GAM inhibits PTPsigma binding to substrate-bound CSPG

The transmembrane tyrosine phosphatase PTPsigma

  • Regulates neurite outgrowth
  • Acts as a nexus for multiple protein and proteoglycan interactions
  • Mediate CSPG inhibition of neurite outgrowth
    • Through binding to the CS side chains of CSPGs
  • HB-GAM has strong binding affinity to the CS and HS chains of proteoglycans
    • HB-GAM might compete with PTPsigma for CS binding
      • Thus reducing the CSPG inhibition.
  • PTPsigma is reciprocally regulated by interactions with CS or HS containing extracellular proteoglycans - proteoglycan switch:
    • Ligated by CS chains
      • PTPsigma inhibits neurite outgrowth
    • Ligated by HS chains
      • Enhances neurite growth
  • HS glycosaminoglycans, such as those on glypican-2
    • Form clusters with PTPsigma
      • Characteristic proposed to drive a localized imbalance of protein tyrosine phosphorylation
        • Promotion of neurite outgrowth
  • Knockdown of PTPsigma in cortical neurons
    • Did not change neurite outgrowth on CSPG in the presence or absence of HB-GAM
    • HB-GAM had similar effects on neurite outgrowth in PTP? knockdown cultures.
  • hal-amu.archives-ouvertes.fr/hal-01468727

HB-GAM

  • Targets the glial scar region
  • Promotes dendritic regeneration in the cerebral cortex.
  • HB-GAM was able to reverse the CSPG inhibition of neurite extension in brain neurons in vitro
  • HB-GAM promotes axonal regeneration through spinal cord injury sites
  • HB-GAM improves dendrite regeneration in injury site after prick-injury in vivo.
  • HB-GAM can promote neurite outgrowth when added to cultures after they have already been inhibited by the CSPG
  • HB-GAM injected into brain tissue can be detected by immuhistochemistry at least until 20 days after the injury.
  • hal-amu.archives-ouvertes.fr/hal-01468727

CS side chains of CSPGs

  • Are major inhibitors of neurite growth in the glial scar
  • CSPGs accumulate in perineuronal nets of the healthy CNS at the end of the critical period of development
  • Their CS side chains are reported to inhibit plasticity underlying behavioral regulation
  • Modulating immune responses
  • Regulation of progenitor cell proliferation
  • hal-amu.archives-ouvertes.fr/hal-01468727

Heart rate variability training



Hyperbaric oxygen therapy


IGF-1

  • Dá se sehnat forma pod jazyk
  • Ev. lze sehnat injekční preparát a kapat ho do nosu nebo inj. s.c. v oblasti léze

Inhibice biosyntezy CSPGs

  • Preventing the deposition of CSPGs by interfering with their biosynthesis
    • Would be an effective approach

CSPG synthesis

  • Creation of a protein core
  • Covalent attachment of numerous glycosaminoglycan (GAG) side chains
  • Introduction of a beta-xylose to a serine or threonine of the core protein
  • Extension from the O4-position of the xylose into a trisaccharide linker
    • Xylose, galactose, galactose
  • Chondroitin sulfate GAG chains
    • Elongated with the repeating beta-(1 › 3)-linked disaccharides
      • Glucuronic acid (GlcA)
      • N-acetyl-galactosamine (GalNAc)
  • Uridine-5'-diphosphate-N-acetyl-galactosamine (UDP-GalNAc)
    • Created from UDP-N-acetyl-glucosamine (UDP-GlcNAc)
      • By the enzyme 4-epimerase through an oxidation and reduction process
  • Per-O-acetylated 4-fluorinated glucosamine analogue 3 - fluorosamine
    • Remarkable ability to perturb GAG biosynthesis
      • Inhibitor to 4-epimerase to prevent GAG elongation
      • May also deplete uridine-5'-triphosphate (UTP) and thus reduce UTP availability for sugar precursors
      • 4-fluoro-substituted N-acetyl-d-glucosamine
        • Converted to the UDP-conjugated form and act as an inhibitor of the 4-epimerase.
  • pubs.acs.org/doi/10.1021/acscentsci.9b00327

Inhibice myozinu II


Inhibiting NOX2 activity after TBI in mice

  • Suppressed microglial neurotoxicity
    • Reduced tissue loss and improved long-term functional recovery (Kumar et al., 2016a,b; Barrett et al., 2017)
  • www.jneurosci.org/content/40/14/2960

Inhibition of CSPG/PTP? signaling

  • CSPGs curtail remyelination through binding with their cognate receptor
    • protein tyrosine phosphatase ? (PTP delta) on oligodendrocyte progenitor cells (OPCs)

Systemically deliverable Intracellular Sigma Peptide (ISP)


Integrin - stimulace

  • The highly charged GAG moieties of CSPGs can interact with these ECM molecules
    • Suppress neurite growth
      • By attenuating integrin activation (Afshari et al., 2010; Tan et al., 2011)
  • Over- expression of integrins
    • Could overcome CSPG inhibition of axon growth (Condic et al., 1999).
  • Thus, CSPGs reduce activity of integrin signaling pathway and activation of integrin signaling overcomes inhibition by CSPGs.

Mangan

Over-expression of kindlin-1

  • Phosphoprotein involved in attachment of actin cytoskeleton to plasma membrane and integrin-mediated function
  • Activates integrin signaling
    • Enhances growth of sensory neurons cultured on aggrecan
    • + regeneration of injured sensory axons across the dorsal root entry zone and into the spinal cord (Tan et al., 2012)

Over-expression of growth-associated protein-43 and/or beta 1 integrin

  • Could partly stimulate regeneration of serotonergic axons on high levels of CSPG
  • Blockade of beta 1 integrin
    • Reduced serotonergic and cortical outgrowth on laminin (Hawthorne et al., 2011)
  • Functional link between laminin/integrins and CSPGs is not specific
    • Integrin activation also inverted neuronal growth suppression by myelin associated inhibitors (Tan et al., 2011).

Interferon gamma

Intracellular PTPsigma Peptides (ISP)

Adult rats with severe thoracic contusive SCI

  • Subcutaneous injections of ISP for 7 weeks induced
    • Significant functional recovery of both locomotor and bladder systems
    • High volume of restored serotonergic innervation to the caudal spinal cord below the level of the lesion
  • Inhibition of PTPsigma with a selective antagonist remarkably promotes axon regrowth and behavioral recovery after SCI.
  • austinpublishinggroup.com/neurological-disorders-epilepsy/fulltext/ajnde-v2-id1010.php

Mice

Knockdown of chondroitin polymerizing factor


Inhibice LAR functions

  • Receptor for CSPGs to inhibit axon regeneration
    • Similar to PTPsigma, LAR also interacts with the GAG chains of HSPGs with high affinity
      • Regulates neuronal functions (Fox and Zinn, 2005; Johnson et al., 2006)
        • Neurite outgrowth in vitro and nerve regeneration (Stepanek et al., 2005; Sun et al., 2000; Wang and Bixby, 1999; Wills et al., 1999; Xie et al., 2001; Yang et al., 2003; Yang et al., 2005; Yang et al., 2006)

LAR phosphatase

  • Another transmembrane receptor of CSPGs (Fisher et al., 2011)
  • LAR is widely expressed in the adult brain and spinal cord
    • Neuronal soma and axon cylinders
  • LAR binds a mixture of purified CSPGs with high affinity
    • First Ig-like domain is critical for CSPG-LAR interactions also through GAG chains of CSPGs
  • CSPG treatment increases activity of LAR phosphatase in vitro

Inhibition of LAR

  • By protein deletion or sequence-targeting blocking peptides
    • Partly enhanced neurite outgrowth of DRG cultures on CSPG substrate (Fisher et al., 2011)
      • But not CNS myelin inhibitors
  • LAR activation due to selective CSPG stimulation in part suppresses extension of neurons.
  • The remaining inhibition by CSPGs after LAR inhibition is probably mediated by other receptors and/or receptor-independent mechanisms (Carulli et al., 2005; Kwok et al., 2011; Shen et al., 2009).
  • LAR protein
    • Was upregulated days to weeks after injury
    • Co-localized to various projection tracts, including serotonergic and CST axons (Fisher et al., 2011; Xu et al., 2015)
  • LAR deletion
    • Increased regrowth of serotonergic axons into the scar tissues and caudal spinal cord
    • After dorsal over-hemitransection at T7
    • Enhanced regrowth of CST fibers into the caudal spinal cord
    • Improved functional recovery by increasing Basso mouse scale locomotor scores and stride length and reducing grid walk errors.
  • LAR plays a crucial role in restricting regrowth of injured CNS axons
  • Pharmacological LAR blockade with sequence- targeting peptides
    • Stimulates regrowth of descending axons and recovery of locomotor function (Fisher et al., 2011).
  • Newly-generated neurons from neuronal restricted precursors
    • Express low levels of PTPsigma and LAR proteins
    • Are intrinsically insensitive to CSPG substrates
  • Secreted factors by cultured neuronal and glial restricted precursors
    • Reduce CSPG inhibition
    • Promote axonal growth in vitro (Ketschek et al., 2012)
  • CSPGs could reduce growth, attachment, survival, proliferation of neural progenitor cells and differentiation of oligodendrocytes through activation of PTPsigma and LAR (Dyck et al., 2015)
  • Lamprey, a type of jawless fish
    • Has heterogeneous neuronal regeneration capabilities after CNS injury
      • Only some descending reticulospinal neurons regenerate after SCI
    • CSPGs are upregulated in the lesioned spinal cord of lamprey
      • PTPsigma and LAR are selectively expressed in bad-regenerating neurons
      • Indicating likely connection between activation of CSPG receptors and poor intrinsic regenerative ability of bad-regenerating neurons in non-mammals (Zhang et al., 2013).
  • austinpublishinggroup.com/neurological-disorders-epilepsy/fulltext/ajnde-v2-id1010.php

LBPS02


Lycium barbarum is a medicinal plant that has been used traditionally in China for thousands of years. Polysaccharides are the main bioactive ingredients of L. barbarum, which plays powerful neuroprotective roles in nervous system diseases through a variety of mechanisms, which has led to increased research (Xing et al., 2016). By purifying functional polysaccharides from L. barbarum, Kou et al. (2017) obtained a new polysaccharide component, named purified L. barbarum polysaccharide (LBPS02). The structure of LBPS02 has been characterized, and its neuroprotective effects investigated. LBPS02 treatments improve cell survival, reduce glutamate-induced mitochondrial dysfunction and ROS accumulation, and protect neurons from damage caused by glutamate stimulation. The mechanism is related to the regulation of extracellular signal-regulated kinases and protein kinase B (Akt) phosphorylation, as well as the inhibition of caspase-dependent mitochondrial signaling. These data suggest inhibitory effects of LBPS02 against glutamate-induced excitotoxicity and indicate the therapeutic potential of LBPS02 in the treatment of NDDs.
  • Neural Regeneration Research 17(9):p 1907-1912, September 2022. | DOI: 10.4103/1673-5374.335142

Laminin

Low energy neurostimulation



Low-intensity pulses US

  • Safety and merits of targeting the thalamus with are currently being examined for severe TBI

Lutein

  • Another strong antioxidant
    • With anti-inflammatory and anti-apoptotic effects
  • Capable of crossing the BBB
  • Protective effects by suppressing
    • Interleukin IL 1beta,
    • IL 6,
    • Monocyte chemoattractant protein 1 expressions

Lycium barbarum polysaccharides

  • Neuroprotective effects
  • Are beneficial for the treatment of AD, PD, and other NDDs
  • Antioxidant, neuroimmunity, anti-apoptotic, autophagy, and other mechanisms (Xing et al., 2016).

Acemannan

  • Main bioactive polysaccharide of Aloe vera
  • Neuroprotective immunomodulator and antioxidant
  • Improves the cognitive performances of middle-aged patients suffering from mental fatigue (Liu et al., 2019)

Ginseng polysaccharides

  • Widely used in the medical field in polysaccharide-based drugs (Yu et al., 2018).

Astragalus polysaccharides

  • Widely used in the medical field in polysaccharide-based drugs (Yu et al., 2018).

Lentinan

  • Widely used in the medical field in polysaccharide-based drugs (Yu et al., 2018).

Fucoidan

  • Widely used in the medical field in polysaccharide-based drugs (Yu et al., 2018).

    • Activated M2 microglia and macrophages

    • Are involved in resolution of inflammation and wound healing through phagocytosis of myelin debris
    • Ability to provide anti-inflammatory and growth promoting factors (Orr and Gensel, 2018; Tran et al., 2018)
    • Anti-inflammatory M2 phenotype has been associated with
      • Improvements in axonal sprouting and regeneration in SCI
      • Oligodendrocyte maturation and remyelination in multiple sclerosis (Miron et al., 2013; Tran et al., 2018)

    M2 macrophages

    • Have an anti-inflammatory and atheroprotective profile
      • By secreting IL-1 receptor agonist, IL-10, and collagen
    • SGLT2 inhibitors have been proven to strongly promote macrophage polarization towards M2
      • Thus alleviate inflammation and atherosclerosis
    • M1 polarized macrophages activate STAT-1
      • Can also be involved in cognitive impairment in Alzheimer’s disease
      • Activated by intracellular Tau accumulation
    • Depletion of perivascular macrophages
      • Prevented short-term memory impairment in a murine model
    • SGLT2 inhibitors may possibly attenuate atherosclerosis and cognitive impairment via macrophages by promoting M2 polarization and downregulating STAT-1

    Murine model, depletion of STAT-1 activation

    • Significantly reduced synaptic dysfunction and cognitive impairment associated with Tau accumulation

    Modafinil

    Study of Modafinil to Treat Fatigue in Persons With Traumatic Brain Injury

    • Dohledat výsledky
    • Modafinil has been shown to be useful for fatigue and sleepiness in patients with
      • Depression, multiple sclerosis, Parkinson's disease
      • Individuals with EDS secondary to a variety of sleep disturbances

    CCa 60 participants with post-TBI fatigue


    Myosin II inhibice

    • An ATP-dependent motor protein, probably mediates CSPG inhibition on axonal growth (Hur et al., 2011; Yu et al., 2012).
    • CSPGs increase phosphorylation of nonmuscle myosin II regulatory light chains
    • Pharmacological or genetic inhibition of myosin II promotes axon growth in vitro on inhibitory substrates including CSPGs and axon regeneration after optic nerve injury (Wang et al., 2020).
    • www.frontiersin.org/articles/10.3389/fncel.2020.00174/full

    Myostimulace

    • K zachování svaloviny
      • Rozpad svaloviny je zátěž na játra a riziko vyšší hladiny amoniaku
        • Který může působit dále neurotoxicky
    • Jaká je hladina CK ?
    • Dochází k rozpadu svaloviny ?
    • Jak ji efektivně stimulovat ? Provádíme to ???

    N-acetylcysteine (NAC) + drug transport inhibitor, probenecid

    • Target, namely the glutathione pathway after severe TBI in children
    • NAC crosses the BBB
    • CSF concentrations that are achieved are only a tiny fraction (pod 0.1%) of those achieved in blood
      • Partly because NAC is rapidly transported back into blood by the organic acid transporters 1 and 3
    • Probenecid inhibits those transporters
      • Thus enhances brain exposure of NAC to levels measurable in human CSF
    • NAC serves both as a direct antioxidant and a source for the synthesis of glutathione
    • Treatment with probenecid and NAC produced a significant alteration in the CSF metabolomic signature of TBI
    • Relative glutathione levels were increased more than 600-fold after treatment with NAC plus probenecid
      • Biochemical processes involving detoxification with glutathione and glutathione recycling were enriched

    Clinical trial in 81 patients

    • NAC was recently shown to have beneficial effects in mild TBI resulting from blast injury in

    NG2 blockade (such as with antibodies)


    Inhibice NG2


    NVG-291

    • Modulates protein tyrosine phosphatase ("PTP delta")
      • Key receptor for chondroitin sulfate proteoglycans ("CSPGs")
    • PTPdelta and CSPGs have been shown to impede repair following injury to the nervous system
      • Spinal cord injury, traumatic brain injury, Alzheimer's disease, multiple sclerosis.
    • NVG-291 promotes neural repair mechanisms
      • Axonal regeneration
      • Remyelination
      • Plasticity
      • Autophagy (a cellular self-cleaning mechanism that removes unnecessary or dysfunctional components)
      • Non-inflammatory phenotype in microglia cells
    • Is restoring life's potential by creating innovative solutions for the treatment of nervous system injury due to trauma or disease as a result of underlying inflammation and/or neurodegeneration. The Company is initially developing drugs for the treatment of multiple sclerosis, spinal cord injury and Alzheimer's disease.
    For further information, please contact:
    NervGen, Vancouver, British Columbia (Newsfile Corp. - September 12, 2021)
    • Huitt Tracey, Corporate Communications, htracey@nervgen.com, 604.362.6209
    • Nancy Thompson, Vorticom Public Relations, nancyt@vorticom.com, 212.532.2208
    • NervGen on Twitter (@NervgenP), LinkedIn (NervGen Pharma Corp.), and Facebook (facebook.com/nervgen/) for the latest news on the Company
    Follow NervGen on Twitter (@NervgenP) and LinkedIn (NervGen Pharma Corp.) for the latest news on the Company.

    NVG-291-R (a close analog to NVG-291)

    • Binding to PTPsigma
      • Led to blockage of the signaling cascade associated with CSPG binding
        • Return of locomotor and urinary functions
    • Reversal of nerve injury
    • Enhanced physiological recovery in acute myocardial infarction
    • Ventral nerve root avulsion
    • Dorsal nerve root crush
    • Enhanced remyelination in a rodent MS models
    • SCI model
    • Immune modulation in SCI models
    • Effects within the peripheral nervous system (PNS)
      • Ability of NVG-291-R to facilitate nerve regeneration and functional recovery following peripheral nerve injury.
    • Significant subset of spinal cord injured animals achieving near complete recovery 100% of spinal cord injured animals
      • Experienced partial to complete recovery of bladder function at the higher doses tested
    • Results were reproduced in multiple studies, labs and preclinical models
      • Including several separate spinal cord injury studies
    • Functional improvement in locomotive and bladder functions was lasting and durable, even after a finite period of daily injections
    • NVG-291-R was found to be relatively simple and non-invasive to administer
    • www.nervgen.com/ptp%CF%83-and-sci/

    Neo kurkumin

    • Firma z Biocevu, ČR - to ve mne vyvolalo pocit důvěry
    • V malé dávce kurkumin stimuluje novotvorbu cév a to by se mohlo hodit pro regeneraci
    • Trochu mne však zaskočila cena a malinkatá velikost tablety - může toto poskytnout dostatečnou dávku ??
    • curcumin-odt-supplement-shrnuti-studie.pdf">mcepharma-shop.s10.cdn-upgates.com/y/y5c5d606b0904e-neo-curcumin-odt-supplement-shrnuti-studie.pdf

    Neuroglobin

    • As an oxygen carrier for transferring oxygen from blood vessels to neurons
      • For satisfying the metabolic needs in mitochondria ...
    • protein found in neurons of both the peripheral and central nervous system
    • Appears to convey some resilience to hypoxic/ischemic insult
      • Perhaps by facilitating oxygen transport across the blood–brain barrier or enhancing availability of oxygen to mitochondria (Chuang et al., 2010)
    • Recently discovered tissue globin widely and specifically expressed in neurons of vertebrate’s central and peripheral nervous systems.
    • Overexpression of neuroglobin
      • Confers neuroprotection against neuronal hypoxia or ischemia-induced damage in cultured neurons and in cerebral ischemic animal models.
    • Several possible neuroprotective roles
      • Ligand binding
      • Oxygen sensing
      • Modulation of cell signaling pathways
      • Maintenance of mitochondria function


    NgR1 inhibice

    • Receptor for three myelin inhibitors Nogo, MAG and oligodendrocyte myelin glycoprotein (Fournier et al., 2001; Fournier et al., 2002; Liu et al., 2006; McGee and Strittmatter, 2003).
    • NgR homologs NgR2 and NgR3 (Lauren et al., 2003; Lauren et al., 2007)
    • NgRs are GPI-linked membrane proteins
    • NgR2 could bind MAG (Venkatesh et al., 2005)
    • NgR1 and NgR3 have been shown to interact with CSPGs
      • Mediate neuronal growth inhibition (Dickendesher et al., 2012)
    • Deletion of both NgR1 and NgR3 in double knockout mice
      • In part overcame CSPG inhibition
      • Increased regeneration of crushed optic nerve axons
    • NgR1 and NgR3 function as additional CSPG receptors
    • Versican-NgR2 interactions appear to mediate plasticity of peripheral sensory fibers at dermo-epidermal junctions (Baumer et al., 2014)
    • NgR2 specifically interacts with C-terminal G3 domain of versican
    • NgR2 deficient nociceptive nonpeptidergic sensory neurons
      • Was less sensitive to inhibition by skin-derived versican.
    • austinpublishinggroup.com/neurological-disorders-epilepsy/fulltext/ajnde-v2-id1010.php

    Ninjurin-2

    • Expression may affect the tolerance of the brain to injury

    Nogo-A inhibice

    • At low levels by radial glia
    • May when induced counteract inhibition of axonal regeneration and sprouting by myelin-associated inhibitors, in particular Nogo-A.

    Olej z čeného kmínu

    • Lžička denně
    • Stimuluje remyelinizaci
    • Snižuje Th1 imunitní reakci
    • Silně protizáněltivý
    • Některé antivirotcké a antimykotické účinky
    • Ps.: tymoquinone - lze dohledat již i jako extrakt i ve vyšší koncentraci




    Overexpressing R-Ras GTPase


    Overexpression of LKB1

    P7C3

    • Neuroprotective compound
    • Promote neurogenesis
    • Protect against neurodegeneration in animal models of neurodegenerative diseases
    %h2 PKC inhibice

    PPARgamma activation

    • Contributes to the ibuprofen-mediated Rho inhibition in neurons (Dill et al., 2010)

    Inhibice PTP sigma

    • GAG chains of CSPG neurocan
      • Binds the first Ig-like domain
      • Through a number of positively-charged amino acids (Aricescu et al., 2002; Shen et al., 2009).
    • PTPsigma is a functional receptor that partially mediates CSPG inhibition of neuronal growth.

    Dorsal Root Ganglion (DRG) neurons cultured from PTPsigma -/- mice

    • Had enhanced neurite growth on CSPG substrate, but not on Myelin Associated Glycoprotein (MAG), a myelin associated axon growth inhibitor

    in vivo study with PTPsigma -/- mice

    • Showed regrowth of lesioned ascending sensory axons in the fasciculus gracilis into CSPG-rich scar tissues (Shen et al., 2009).

    Adult PTPsigma deletion mice with T9 hemisection

    • Regrowth of Corticospinal Tract (CST) axons into the caudal spinal cord (Fry et al., 2010)

    PTPsigma deletion

    Loss of PTPsigma

    • Enhanced nerve regeneration following spinal cord injury (SCI)
    • Chemoresistance in cultured cancer cells
    • Hyperactive autophagy
      • Critical to cell survival
      • Clearance of pathological aggregates in neurodegenerative diseases
    • Modulation of PTPsigma may provide therapeutic value in a variety of contexts

    Palmitoyl ethanolamide

    • Studied for its ability to reduce several inflammatory processes
      • Involving the central nervous system
    • Restoring correct functioning of the central nervous system
    • Ability to modulate the function of the neuromuscular junction
      • By binding to acetylcholine receptors in different experimental conditions

    Several studies ultra-micronized palmitoyl ethanolamide

    • Interesting nutraceutical support for the treatment of pathological neuromuscular conditions,
    • Specifically when the normal activity of the acetylcholine receptor is altered

    Multicentric clinical trials are needed

    • To confirm the efficacy of ultra-micronized palmitoyl ethanolamide in improving symptoms of neuromuscular diseases
    • Literature reviewed here strongly supports the ability of this endocannabinoid-like molecule to modulate the acetylcholine receptors

    Phosphatidil cholin

    • To by mohla být důležitá složka pro regeneraci mozku
    • Netoxický potravní doplněk

    Phosphatidylserine

    Phosphorylation (pTRKB)

    • Součástísignalizace BDNF
    • PTPRS - receptor for CSPGs, interacts with TRKB and restricts TRKB phosphorylation

      • Piracetam (Geratam)


      Placenta derived growth factor (PLGF)

      • PLGF encodes three isoforms: PLGF-1, PLGF-2, PLGF-3.
      • PLGF can bind both VEGFR-1 and VEGFR-2.
      • Flt1 and PLGF have a potent and persistent effect on vessel formation.
      • PLGF stimulates the formation of vessels in ischaemic heart disease, and anti-Flt1, by blocking PLGF effect, can inhibit the neovascularisation in the ischaemic retina and tumours.
      • PlGF and Flt1 also play a critical part in the recruitment and homing of circulating endothelial progenitor cells (CEPs) and support monocyte recruitment for vasculogenesis at the site of ischaemia and in tumours
      • pmj.bmj.com/content/81/954/236

      Povídání

      Preventing GAG sulfation of CSPGs

      • Removes much of their inhibitory activity on axon growth in vitro (Gilbert et al., 2005; Sherman and Back, 2008; Wang et al., 2008)
      • GAG sulfation patterns are important for CSPG function
      • CSPGs might non-specifically impede binding of some ECM molecules to their cell surface receptors through steric interactions
      • Two transmembrane proteins of the LAR phosphatase subfamily,
        • Protein Tyrosine Phosphatase ? (PTP?)
        • LAR
      • Function as the receptors by binding CSPGs with high affinity and mediating CSPG inhibitory effects
        • (Fisher et al., 2011; Shen et al., 2009; Xu et al., 2015).
      • CSPGs may act by binding to Nogo Receptor 1 (NgR1) and NgR3
        • Receptors known for myelin-associated inhibitors (Dickendesher et al., 2012)
      • CSPGs block axon regeneration
        • Likely by multiple molecular mechanisms, making them especially potent and difficult therapeutic targets
      • austinpublishinggroup.com/neurological-disorders-epilepsy/fulltext/ajnde-v2-id1010.php

      Pro Brain Fuel

      • Čistý MCT C8 olej lisovaný z organických kokosů
      • Z 98,6% kyselinou kaprylovou (C8)
        • Nejčistší zdroj ketonů – pohotového zdroje energie pro váš fyzický a mentální výkon.
      • 519 Kč

      ProBrain

      • Vitamín B6 (pyridoxinhydrochlorid) 5 mg 110
      • Vitamín B9 (folát) 200 mcg 100
      • Vitamín B12 (kyanokobalamin) 7.5 mcg 160
      • Zinek (diglycinát zinečnatý) 5 mg 50
      • Citikolin sodný 250 mg +
      • Bakopa drobnolistá (Bacopa Monnieri) – extrakt (10 % bakosidů) 200 mg +
      • Korálovec ježatý (Hericium erinaceus / en. Lion’s Mane) – extrakt z plodnice (20 % polysacharidů) 350 mg +
      • Sharp PS® SF-60P (Fosfatidylserin) 125 mg +
      • L-tyrosin 200 mg +
      • L-theanin 100 mg +
      • Rozchodnice růžová (Rhodiola rosea) – extrakt z kořene (3 % salidrosidů) 50 mg +
      • Borovice přímořská (Pinus pinaster) – extrakt z kůry – 75mg (95 % proanthokyanidinů) 75 mg +
      • Meduňka lékařská (Melissa officinalis)
      • (2,5 % kyselina rozmarýnová)

      Probiotics

      Progesteron

      • Forma progesteronu, která nestimuluje glukokortikoidní receptory ani testosteronové
        • Spojena s neurogenezí
      • Podání
        • Během chronického stavu
        • A jenom některých forem progesteronu
        • Ideálně v kombinaci s vhodnou chemickou formou estrogenu stran neurogeneze a neuroregenerace
        • Efekt na neuroregeneraci může být jiný u žen a u mužů

      Efficacy and Safety Study of Intravenous Progesterone in Patients With Severe Traumatic Brain Injury (SyNAPSe)

      • Neuroprotective properties
      • Promote neurogenesis
      • Protect against neurodegeneration in animal models of traumatic brain injury

      ROCK inhibitors

      • Enhanced axon regrowth
      • Provided neuroprotection in different models of neurological disorders (Kubo and Yamashita, 2007; Fujita and Yamashita, 2014).

      Fasudil and its derivatives (hydroxyfasudil and dimethylfusudil)

      Y-27632

      Y-39983

      Systemic application of RPTP peptides

      • Efficiently blocks CSPG function in contrast to the highly invasive approach of applying ChABC locally
      • Receptor blockade should also avoid the issues of incomplete digestion of CSPGs and digestion of other sulfated proteoglycans
      • Highly sulfated proteoglycans in the scar or PNN halt the attempt of axons to regenerate
      • Multiple factors are responsible for neural repair failure after CNS injury
        • Combining CSPG receptor blockade with other strategies, such as cell transplants, probably becomes more effective.
      • austinpublishinggroup.com/neurological-disorders-epilepsy/fulltext/ajnde-v2-id1010.php

      Reduction of RhoA transcripts in axons

      Inhibice RhoA a aktivace Akt

      Inhibitors of RhoA and ROCK

      Remyelin cps.30

      • Uridinu, palmitoyletanolamidu, vitamínů skupiny B, vitaminu C a biologicky aktivní kyseliny listové.

      Repulsive guidance molecule A (RGMa)

      • A GPI-linked glycoprotein,
      • Inhibits axon growth
        • By interacting with its neuronal receptor neogenin
      • Promotes reactive astrogliosis and glial scar formation
        • By activating the TGFbeta 1-Smad2/3 signaling pathway
          • Preventing neurological functional recovery after stroke (Zhang et al., 2018)

      Treatments with RGMa antibodies

      Pharmacological RhoA inhibition by C3 transferase and some nonsteroidal anti-inflammatory drugs

      Hlodavci

      • Stimulates axon growth,
      • Overcomes CSPG suppression
      • Improves behavioral recovery in rodents with SCI (Dergham et al., 2002; Dill et al., 2010; Fournier et al., 2003; Fu et al., 2007; Xing et al., 2011)

      Phase I/IIa clinical trial of an inhibitor of RhoA

      • Blocking either RhoA or ROCK with inhibitors
        • Overcomes growth inhibition by CSPGs and other inhibitors (Borisoff et al., 2003; Mueller et al., 2005)
        • Enhances axon regeneration and functional recovery after CNS axon injury in rodents (Fournier et al., 2003)
      • Knockdown of RhoA in lamprey reticulospinal neurons by retrogradely-delivered morpholinos
        • Inhibited retrograde apoptotic signaling and axon retraction and promoted axon regeneration after SCI (Hu et al., 2017).
      • www.frontiersin.org/articles/10.3389/fncel.2020.00174/full

      Bacterial C3 transferase and its derivatives

      • Have been frequently used as selective inhibitors of Rho
      • By ADP-ribosylating the Rho effector domain and blocking Rho function

      SCI and optic nerve crush in rodents

      • C3 treatment
        • Prevents cell loss
        • Promotes axon regeneration after
      • (Lehmann et al., 1999; Dergham et al., 2002; Dubreuil et al., 2003)

      Modified C3 that is cell-permeable (Cethrin, BA-210, and VX-210)

      SCI rodents

      Recombinant fusion protein containing C3

      SCI rodents

      • Inactivated RhoA in the lesioned spinal cord
      • Reduced secondary tissue damage and glial scarring
      • Stimulated axon regeneration and functional recovery
      • Even when applied 16 days after injury (Lord-Fontaine et al., 2008)

      C3-peptides

      siRNA

      Ibuprofen

      • (Fu et al., 2007; Boato et al., 2010; Dill et al., 2010; Gwak et al., 2017)

      Rho inhibitor C3 VX-210

      phase I/IIa clinical trial of VX-210 completed with acute SCI (NCT00500812; Fehlings et al., 2011; McKerracher and Anderson, 2013)

      • 48 acute traumatic cervical and thoracic SCI patients
      • Received a single dose of VX-210 (range: 0.3–9.0 mg) to the spinal cord dura mater during decompression surgery
      • Within the first 7 days after injury
      • Results suggested the tolerability of the treatment
      • Improvement in motor strength in patients with cervical SCI
      • Recovery trajectory of thoracic SCI cases was similar to that in natural history studies

      Phase IIb/III SPRING (SCI Rho inhibition investigation) trial for acute traumatic cervical SCI (NCT02669849)

      • Major goal of this randomized, double-blind, placebo-controlled trial was to evaluate its
        • Safety and efficacy in promoting functional recovery by Rho inhibition (Fehlings et al., 2018)
      • Terminated by Vertex probably because of lack of efficacy after an interim analysis.

      Ibuprofen, indomethacin, and sulindac sulfide

      • Inhibit Rho activity independently of their classical function as the inhibitors of cyclooxygenases
      • Promote axon regrowth and functional recovery after SCI in rodents (Zhou et al., 2003; Fu et al., 2007; Wang et al., 2009)

      Meta-analysis of multiple preclinical studies on the effects of Rho-inhibiting NSAIDs

      • Suggested a moderate effect on motor recovery after ibuprofen or indomethacin treatment (Watzlawick et al., 2014)
      • NSAIDs are widely used clinically for relieving pain and treating various disorders
        • Especially attractive to test Rho-inhibiting NSAIDS, including ibuprofen, as treatments for CNS axonal injuries

      A phase I clinical SCISSOR (SCI study on small molecule-derived Rho inhibition) trial

      • Initiated to treat acute SCI with high-dose ibuprofen (NCT02096913; Kopp et al., 2016)
      • Key inclusion criteria include acute traumatic motor-complete SCI (classified as AIS A or AIS B) with lesions at the levels of C4-Th4
      • Evaluate the safety, feasibility, and pharmacokinetics of ibuprofen when used at the high dose of 2,400 mg per day
      • Preclinical studies showed potent Rho inhibition by ibuprofen when applied at high doses
        • 50–70 mg/Kg body weight
        • Zhou et al., 2003; Fu et al., 2007; Wang et al., 2009

      GSK-3beta inhibitors - lithium

      • Overcome the growth suppression of CNS inhibitory substrates
      • Promoted axonal regeneration and functional recovery in adult rodents with SCI (Dill et al., 2008)
      • Commonly used to treat bipolar illness
      • Interesting potential therapeutic approach for promoting axon regrowth and functional recovery after CNS injuries (Dill et al., 2008; Ohtake et al., 2016)
      • Enhanced proliferation and neuronal differentiation of neural progenitor cells in the spinal cord of adult rats (Su et al., 2007).

      A phase I clinical trial was completed to evaluate the safety and pharmacokinetics of lithium in chronic SCI patients (NCT00431171)

      • Trial suggests that lithium is safe for treating chronic SCI patients (Wong et al., 2011)

      A randomized, double-blind phase II clinical trial

      • Evaluate its efficacy for treating chronic SCI patients (NCT00750061; Yang et al., 2012)
      • Lithium was effective for reducing neuropathic pain in chronic SCI
        • But did not improve the neurological outcomes of patients

      Clinical trials with combined strategies, including

      • Transplanting umbilical cord blood-derived mononuclear cells
      • Oral lithium
      • Methylprednisolone
      • Followed by locomotor training
      • Improved both motor and autonomic functions in some SCI patients (NCT01046786 and NCT01354483; Zhu et al., 2016)

      Riboflavin - vitamin B2

      • Další vit. B, který je důležitý pro nervovou soustavu

      Rivastigmine

      Ropirinol

      • Byl neuroprotektivní u buněk ALS
      • Snesl by sympatický systém malé dávky a ev. jejich pomalé navyšování ?
        • Frekvence srdce, dechové centrum ??

      S100B protein

      • Is a calcium-binding protein produced by glial cells
      • S100B protein has been detected in serum after the opening of the BBB after brain injury.
      • S100B shows a dose-dependent dual effect in neurons.
      • In small doses
        • S100B acts as a neurotrophic factor for neuroprotection
      • High doses
        • S100B increases neuroinflammation and worsens the neural survival.
      • Mohl by sloužit jako biomarker pokračující regenerace ?

      Schisandra chinensis polysaccharide


      Schisandra chinensis (Turcz.) Baill is a traditional Chinese medicine commonly used for treating forgetfulness or dementia. Schisandra chinensis polysaccharides (SCPs) are the main bioactive components in the mature and dried fruit of Fructus schisandra. In an animal model of AD, SCP improves the cognition and histopathological changes in AD mice, decreases the levels of pro-inflammatory cytokines and reduces the activation of astrocytes and microglia in the hippocampus (Xu et al., 2019). The anti-AD effects of SCP were achieved mainly by activating the NF-?B/MAPK pathway to alleviate neuroinflammation. Subsequently, the homogeneous heteropolysaccharide SCP2-1 was isolated and purified from the SCPs, and its effects on microglial activation and neuroinflammation were examined in cultured cells and the LPS-induced mouse model (Xu et al., 2020a). In vitro experiments showed that SCP2-1 reverses the LPS-induced microglial polarization by upregulating lipoprotein receptor-related protein-1 and inhibiting the over-activation of NF-?B and c-Jun N-terminal kinase pathways. In addition, the in vivo experiment showed that SCP2-1 ameliorates LPS-induced cognitive impairment and neuroinflammation in mice. Moreover, Xu et al. (2020b) revealed the preliminary structure of SCP2-1 and found that the anti-neuroinflammatory activity of SCP2-1 was related to the high glucose and galactose contents and the structural characteristics of the major bonds of glucose residues (1›4)-?-D-GLC and (1›4)-ß-D-GALP. These findings suggest that SCP is a potential candidate for the prevention and treatment of AD.

      Suppression of OASIS and C6ST1


      TBI-10

      • A compound derived from omega-3 fatty acids
      • Promote neurogenesis and protect against neurodegeneration in animal models of traumatic brain injury.

      TUDCA

      • Neuroprotektivní má zajímavé efekty i u ALS

      Thymosin beta 4 (Tbeta4)

      • Is an important G-actin-sequestering molecule in cells

      In animal models Tbeta4 injection

      • Increases proliferation of NPCs
      • Enhances angiogenesis
      • Promotes NPC differentiation

      Tolcapone

      • Catechol-O-methyl-transferase (COMT) inhibitor

      A Trial Evaluating Effects of COMT Inhibition in Patients With Acquired Brain Injury

      Transcranial magnetic stimulation (TMS)

      • Potential of repetitive TMS (rTMS) as an intervention for traumatic brain injury
      • Painless method to stimulate the human brain
      • Repeated applications of TMS can influence brain plasticity and cortical reorganization
        • Through stimulation-induced alterations in neuronal excitability
      • Existing evidence has demonstrated positive outcomes in people with
        • Motor disorders
        • Psychiatric conditions
      • May be a promising treatment for people with traumatic brain injury.
      • www.researchgate.net/publication/6811561_Transcranial_Magnetic_Stimulation_A_Possible_Treatment_for_TBI

      A 6-week rTMS protocol (30 sessions) to a 26-year-old man who remained in a vegetative state 287 days after severe TBI

      • Stimulation was directed over the right dorsolateral prefrontal cortex
      • Repeated safety measures, neurobehavioral assessments, clinical examinations, and evoked potentials (EP) were obtained at baseline, every fifth rTMS session (weekly), and at a 6-week follow-up.
      • There were no adverse events related to the provision of rTMS treatment.
      • A trend toward significant (P 5 .066) neurobehavioral gains
        • Temporally related to provision of rTMS
      • Left-sided brain stem auditory EP wave V latencies and waves I to V interpeak latencies
        • Improved along with neurobehavio-ral gains during provision of rTMS
        • Suggesting that improved neural conduction in the pathway mediated the neurobehavioral improvements
      • Repetitive TMS merits further investigation as a safe therapeutic intervention to alter neural activity, to modulate neural activity, and/or to facilitate recovery in persons with disordered consciousness subsequent to severe TBI.
      • www.researchgate.net/publication/240211532_TMS-associated_neurobehavioral_gains_during_coma_recovery

      Intermittent theta burst stimulation (iTBS)

      Animal model of pediatric TBI (postnatal day 16-17)

      • Injury results in abnormal neuronal hypoactivity
        • In the non-injured primary somatosensory cortex (S1)
      • Reshaping the abnormal post-injury neuronal activity may provide a suitable strategy to augment rehabilitation.
      • High-frequency, non-invasive transcranial magnetic stimulation (TMS) 2x a week over a four-week
      • TBI rats subjected to TMS therapy showed
        • Significant increases in the evoked-fMRI cortical responses (189%)
        • Evoked synaptic activity (46%)
        • Evoked neuronal firing (200%)
        • Increases expression of cellular markers of neuroplasticity in the non-injured S1
          • Compared to TBI rats that did not receive therapy
        • Rats showed less hyperactivity in behavioral tests
      • TMS as a promising approach for reversing the adverse neuronal mechanisms activated post-TBI.
        • Could readily be translated to human studies.
      • www.researchgate.net/publication/282644980_Transcranial_magnetic_stimulation_facilitates_neurorehabilitation_after_pediatric_traumatic_brain_injury
      • Repetitive transcranial magnetic stimulation
        • Promotes neurological functional recovery in rats
        • With traumatic brain injury by upregulating synaptic plasticity-related proteins
        • February 2023Neural Regeneration Research 18(2):368
      • www.researchgate.net/publication/366760983_Repetitive_transcranial_magnetic_stimulation_promotes_neurological_functional_recovery_in_rats_with_traumatic_brain_injury_by_upregulating_synaptic_plasticity-related_proteins

        • Trehaloza


        Vision therapy

        Acetyl-l-carnitine inositol

        Agonisté cholinergního systému

        An upregulated cholinergic system

        • May account for a quasi-normal daily amount of W in HDC or H1-receptor KO mice
        • Likely constitutes a major compensatory mechanism when the brain is facing deficiency of an activating system.
        • pubmed.ncbi.nlm.nih.gov/26723880/

        Aerobic exercise

        • Promotes adult neurogenesis
        • By increasing the production of neurotrophic factors
          • Brain-derived neurotrophic factor (BDNF)
          • Insulin-like growth factor 1 (IGF-1)
          • Vascular endothelial growth factor (VEGF)
        • Exercise-induced neurogenesis in the hippocampus
          • Associated with measurable improvements in spatial memory
        • Consistent aerobic exercise over a period of several months
          • Induces marked clinically significant improvements in executive function
            • Cognitive control of behavior
            • Increased gray matter volume in multiple brain regions
              • Particularly those that give rise to cognitive control
          • Greatest improvements in gray matter volume in response to aerobic exercise are
            • Prefrontal cortex
            • Hippocampus
          • Moderate improvements
            • Anterior cingulate cortex
            • Parietal cortex
            • Cerebellum
            • Caudate nucleus
            • Nucleus accumbens [1]

              • Alpha-lipoic acid

              • Lowers oxidative stress at the blood-brain barrier (BBB)
              • Excellent antioxidant source
              • Anti-inflammatory and antioxidant properties
              • Help reduce edema and preserve BBB permeability following a brain injury
              ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller “Inside-Out Health,” and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science degree in human nutrition. The ACA Sports Council named him “Sports Chiropractor of the Year” in 2015. He is on the advisory board for the Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A frequently published author in peer-reviewed journals and other mainstream publications, he is a thought leader in his field and practice. His new book, “Superhighway to Health,” was published in June 2021. He can be reached at drrobertsilverman.com.

              Amanita caesarea polysaccharide


              Amanita caesarea is a fungi of the Amanita genus that is distributed in the Sichuan and Yunnan provinces of China. Zhu et al. (2016) isolated a water-soluble heterosaccharide (AC-1) from the fruitbody of A. caesarea, characterized its chemical structure, and evaluated its antioxidant activity. AC-1 is mainly composed of ?-D-glucose and ?-D-lyose in at a 2:1 ratio. The main chains are 1,4-alpha-D-glucose and 1,36-alpha-D-glucose, and the branch chain has a 1-alpha-D-lyxose residue. The in vitro experimental results of this study also showed that the A. caesarea polysaccharide exhibits a strong antioxidant activity. Li et al. (2019b) isolated and purified new polysaccharides, named A. caesarea polysaccharides (ACPs), that have different compositions and structures than AC-1 isolated from the fruitbody of A. caesarea, and they investigated the relationship between its neuroprotective effect and antioxidant activity. The data from both in vivo and in vitro experiments showed that ACPs have significant neuroprotective effects and anti-AD activities. The mechanisms are mainly related to the regulation of Nrf2-mediated oxidative stress. Although there are differences in the monosaccharide compositions and chemical structures between AC-1 and the ACPs, they all show promising antioxidant activities, suggesting that the polysaccharides of A. caesarea have the potential to protect the brain from neuronal damage caused by oxidative stress.

              Ananas

              • Denně jedna proce
                • Papain, bromelain - šance na snížení tvorby gliové jizvy ???
                  • Umí natrávit chondroitin sulfát...

              Annona muricata L. polysaccharide

              • ALP0 is a polysaccharide component extracted from A. muricata leaves
                • Consists of galactose (64.3%), glucose (25.37%), mannitose (9.81%), caramelized sugar (0.51%), glucosamine (0.93%), and galactosamine (0.06%)
              • Neuroprotective effects of Annona muricata L. Polysaccharide (ALP)
                • Oxidative stress model of hippocampal neurons
              • Kim et al. (2020) reported that ALP protects a hippocampal neuronal cell line (HT22) from H2O2-induced oxidative stress
                • By directly inhibiting H2O2-induced ROS production
                  • Inhibiting excessive MAPK and NF-?B signaling
                  • Activating PI3K/Akt-mediated activation of Nrf2 signaling
              • Findings suggest that ALP may be the basis for new candidate drugs in the treatment of NDDs.

              21-amino-steroids

              Green tea extract

              Ginkgo biloba extract

              Resveratrol

              Curcumin

              Niacin


              Astaxanthin

              Stretch injury model of TBI using astrocyte cultures

              • Attenuated apoptosis by inhibiting NKCC1 expression
              • Reduced the expression of NF-kappaB-mediated pro-inflammatory factors

              Mice, intraperitoneal injection of astaxanthin

              • 10, 25, 50, or 100 mg/kg body weight 30 min after impact
              • Decreased TBI-related brain tissue injury (induced by CCI)
                • Dose-dependently ameliorating AQP4/NKCC1-mediated cerebral edema
              • Highest dose examined was shown to improve neurologic deficits and the BBB permeability

              Animals received a left frontal TBI using a weight-drop device

              • Astaxanthin (25 or 75 mg/kg) to mice via oral gavage
              • Beginning 30 min post-trauma
              • Followed by six additional daily oral gavages
              • Astaxanthin administration improved sensorimotor performance
              • Enhanced cognitive recover
              • Reduction of lesion size in the cortex and expressions
                • Comparable to controls of brain-derived neurotrophic factor (BDNF)
                • Growth-associated protein-43 (GAP-43), synapsin, and synaptophysin (SYP)
                • Indicating the induction of neuronal survival and plasticity, were recorded

              Berberine

              • In certain herbs, such as coptis and berberis
              • Promote neurogenesis and neuroplasticity.

              Betagulukany

              • Od Mycomedica / Zinzino Extend / ...
              • Sníží riziko vzniku infekčních komplikací, zvýší šanci na jejich přežití pokud vzniknou

              Bexarotene

              -inhibited apoptosis and inflammation

                • By upregulating the lncRNA Neat1

              Mice

              • Improved the neurological functions of mice after TBI
                • Through apolipoprotein E

              NSAIDS na Bolest hlavy

              • Increasing animal based evidence suggests that mild TBI is related to brain cell injury
                • Caused by overexpression of a cellular enzyme (COX-2) that causes neuroinflammation
              • Fortunately, inhibition of COX-2 is easily achieved using ibuprofen
              • Hypothesize
                • Head injured patients treated with ibuprofen will have a lower incidence of mild TBI symptoms than patients treated with acetaminophen

              Randomized clinical trial - zrušen pro málo pacientů

              • Nicméně dlouhodobě prozánětlivý stav v CNS po poranění může blokovat neurogenezi a neuroregeneraci
                • Bude mít smysl zaměřit se na protizáněltivé prvky ve stravě

              Cannabinoids

              • Anti-inflammatory properties
              • Reduce neurogliosis in animal models

              Carotenoids

              • Class of pigments synthesized by plants, algae, and photosynthetic bacteria
              • 8 isoprene units with a total of 40 carbon atoms
              • Over 1100 known carotenoids,
              • Class of carotenoids containing oxygen (xanthophylls)
              • Class of oxygen-free, purely hydrocarbon carotenoids (carotenes)
              • Human brain, various carotenoids, including
                • -carotene, -carotene, -carotene, -cryptoxanthin, lutein, and zeaxanthin
                • Carotene, -carotene, -carotene, -cryptoxanthin
                  • Can be converted into vitamin A
                  • Directly involved in the mechanism of vision, ensuring adequate retinol formation
              • Antioxidants and anti-inflammatory properties, modulatory activities of autophagy

              Celastrol

              • A compound found in plants of the thunder god vine
              • Promote neurogenesis and protect against neurodegeneration in animal models

              Cell-based therapies

              • Transplants of various cell types such as neural stem cells, olfactory ensheathing cells, and mesenchymal stem cells have shown promise in animal models for promoting neuroregeneration and restoring neurological function after injury.

              Enzyme chondroitinase ABC

              Focal traumatic spinal cord injury

              • Injected directly into the lesion to remove the glycosaminoglycan (GAG) chains of CSPGs
                • Crucial component of their inhibitory action
              • CSPG inhibition of the morphological differentiation of OPCs cannot be overcome by promising pro-remyelinating therapies
              • pubs.acs.org/doi/10.1021/acscentsci.9b00327

              Treatment with ChABC in vitro

              • Could remove up to 88% of sulfated GAGs of CSPGs (Henninger et al., 2010)
              • Remarkably enhance neurite outgrowth in neurons cultured on CSPG substrates (Busch et al., 2009; Kigerl et al., 2009)

              Local administration of ChABC to injured CNS in vivo

              • Has been widely employed to promote regeneration of lesioned axons and collateral sprouting of spared axons (Bradbury et al., 2002; Crespo et al., 2007; Fawcett, 2006; Jefferson et al., 2011)
              • ChABC application has been reported to promote regrowth of axons and formation of synaptic contacts along a number of axonal pathways
                • Including corticospinal,
                • Serotoninergic,
                • Reticulospinal,
                • Nigrostriatal
                • Ascending sensory axons
                • Clarke’s nucleus neurons (Barritt et al., 2006; Bradbury et al., 2002; Fouad et al., 2005; Garcia-Alias et al., 2009; Garcia-Alias et al., 2011; Moon et al., 2001; Tom et al., 2009; Yick et al., 2000)

              Transgenic expression of ChABC in reactive astrocytes

              • Promote regrowth of lesioned descending CSTs
              • Ascending sensory fibers in the spinal cord (Cafferty et al., 2007).

              ChABC treatment

              • Additive effects when combined with other regenerative strategies
                • Transplants of different types of cells or biomaterials
                • Applications of neurotrophic factors
                • Compounds that block myelin inhibitors
                • Other effective approaches (Alilain et al., 2011; Bradbury and Carter, 2011; Chau et al., 2004; Crespo et al., 2007; Fouad et al., 2005; Garcia-Alias et al., 2009; Garcia-Alias et al., 2011; Houle et al., 2006; Ikegami et al., 2005; Mingorance et al., 2006; Tom et al., 2009)

              CSPG digestion by local ChABC at the edge of cell transplants

              • Could facilitate axon exit from the grafts into the spinal cord (Alilain et al., 2011; Fouad et al., 2005; Tom et al., 2009).

              Combined ChABC and nerve autograft

              • Resulted in longer regeneration of serotonin and other projection tracts and better recovery of functions after SCI

              Transplanted Schwan cells genetically modified to secrete ChABC and a neurotrophin

              • Into subacutelycontused spinal cord in rats
              • Enhanced regrowth of multiple axonal tracts
                • Propriospinal, CST, 5-HT and other brainstem projecting fibers
                • Into and caudal to the grafts - number of myelinated axons, thus promoting recovery of locomotor and sensory functions (Kanno et al., 2014).
              • Digestion of GAG chains by ChABC is the major molecular basis to overcome CSPG function
                • Enzyme may facilitate recovery after CNS injuries through other mechanisms
                  • Upregulation of tissue plasminogen activator and plasmin
                  • Altered orientation of astrocytic processes to guide elongation of regenerating axons (Milbreta et al., 2014)
                  • Activated M2 macrophages
                  • Remodelling of specific CSPGs
                  • Promoting deposits of laminin
                  • Enhancing vascularity around lesion (Bartus et al., 2014)
              • austinpublishinggroup.com/neurological-disorders-epilepsy/fulltext/ajnde-v2-id1010.php

              Small Interference RNA Targeting Connexin-43

              • Improves Motor Function and Limits Astrogliosis After Juvenile Traumatic Brain Injury.
              • ASN Neuro. 2019 Jan-Dec;11:1759091419847090. doi: 10.1177/1759091419847090. PMID: 31194577

              Constraint-induced movement therapy

              Functional electrical stimulation

              Treadmill training with body-weight support


              Coptis chinensis Franch. polysaccharide
              Coptis chinensis Franch. is a long-used traditional Chinese medicine. Its ability to alleviate symptoms of NDDs have been clinically confirmed. Applications of C. chinensis Franch polysaccharide (CCP), a water-soluble polysaccharide isolated from the dried rhizome of C. chinensis Franch, can greatly prolong the lifespan of Caenorhabditis elegans, decrease the rate of paralysis, reduce Aß deposition in the head, and upregulate the small heat-shock proteins against Aß-induced neurotoxicity (Li et al., 2018). The neuroprotective activities of CCP and its possible mechanisms against Aß25–35-induced cytotoxicity have been further validated in PC12 cells (Li et al., 2019a). CCP also exhibits great neuroprotective effects in Aß25–35-treated PC12 cells, and the mechanism is related to the c-Jun N-terminal kinase-mediated apoptotic signaling pathway. Further studies in animal models are required to determine the potential of CCP as a drug candidate for AD therapy.
              • Neural Regeneration Research 17(9):p 1907-1912, September 2022. | DOI: 10.4103/1673-5374.335142

              Corydalis yanhusuo polysaccharide


              Corydalis yanhusuo W.T. Wang is a well-known traditional Chinese medicine commonly used to relieve pain. While the biological activities of C. yanhusuo alkaloids and their derivatives have been extensively explored, there are limited studies on the bioactivities of the polysaccharide components. He et al. (2020) isolated a highly purified water-soluble neutral polysaccharide from the plant, named C. yanhusuo polysaccharide (CYP). The CYP treatments protect cells from Aß25–35-induced cytotoxicity, reduce the release of lactate dehydrogenase and mitochondrial cytochrome c, mitigate mitochondrial dysfunction, and reverse increases in the Bax and Bcl-2 protein expression ratio, which leads to a remarkable dose-dependent elevation of cell viability. Thus, the neuroprotective effects of CYP may be achieved by inhibiting Aß-induced apoptosis through the mitochondrial apoptotic pathway, which indicates the therapeutic potential of CYP against AD.
              • Neural Regeneration Research 17(9):p 1907-1912, September 2022. | DOI: 10.4103/1673-5374.335142

              Crocin

              • Has shown neuroprotective effects
              • Partially dependent on the activation of Notch signalling

              D-cycloserine

              • Antibiotic and partial agonist of the NMDA receptor
              • Promote neurogenesis and neuroplasticity in animal models.

              Dancing molecules

              • Stupp’s new breakthrough therapeutic
              • Can find and properly engage constantly moving cellular receptors
              • Injected as a liquid
              • Immediately gels into a complex network of nanofibers that mimic the extracellular matrix of the spinal cord
              • By matching the matrix’s structure
                • Mimicking the motion of biological molecules and incorporating signals for receptors
                • The synthetic materials are able to communicate with cells.
              • “Receptors in neurons and other cells constantly move around,” Stupp sai
              • “The key innovation is to control the collective motion of more than 100,000 molecules within our nanofibers.
                • By making the molecules move, ‘dance’ or even leap temporarily out of these structures, known as supramolecular polymers
                  • They are able to connect more effectively with receptors.”
              • Fine-tuning the molecules’ motion within the nanofiber network
                • Make them more agile
                • Resulted in greater therapeutic efficacy in paralyzed mice
              • Formulations of their therapy with enhanced molecular motion
                • Performed better during in vitro tests with human cells
                • Indicating increased bioactivity and cellular signaling.
              • “Given that cells themselves and their receptors are in constant motion
                • You can imagine that molecules moving more rapidly would encounter these receptors more often,” -Signals mimic natural proteins
              • Once connected to the receptors, the moving molecules trigger two cascading signals
                • Critical to spinal cord repair
                • Prompts the long tails of neurons in the spinal cord, called axons, to regenerate
                • Helps neurons survive after injury
                  • Causes other cell types to proliferate, promoting the regrowth of lost blood vessels that feed neurons and critical cells for tissue repair
                  • Induces myelin to rebuild around axons and reduces glial scarring
              • “Our synthetic signals are short, modified peptides
                • When bonded together by the thousands — will survive for weeks to deliver bioactivity
              • End result is a therapy that is less expensive to produce and lasts much longer.”
              • Could be used to prevent paralysis after major trauma
                • Automobile accidents, falls, sports accidents and gunshot wounds
              • As well as from diseases
                • “supramolecular motion” is a key factor in bioactivity
                  • Can be applied to other therapies and targets.
                  • Similar to those in the brain affected by stroke and neurodegenerative diseases
                    • ALS, Parkinson’s disease and Alzheimer’s disease,” Stupp said
              • Northwestern study authors include Evangelos Kiskinis, assistant professor of neurology and neuroscience in Feinberg; research technician Feng Chen; postdoctoral researchers Ivan Sasselli, Alberto Ortega and Zois Syrgiannis; and graduate students Alexandra Kolberg-Edelbrock, Ruomeng Qiu and Stacey Chin. Peter Mirau of the Air Force Research Laboratories and Steven Weigand of Argonne National Laboratory also are co-authors.
              • Simpson Querrey Institute for BioNanotechnology (SQI) and its affiliated research center, the Center for Regenerative Nanomedicine. He has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine.
              • news.northwestern.edu/stories/2021/11/dancing-molecules-successfully-repair-severe-spinal-cord-injuries/
              • Advanced Photon Source

              Paralyzed mice can now “walk” once again.

              • Injectable treatment for spinal cord injury
              • Molecules that prompt spinal cells to respond by healing
              • Used X-ray characterization at the Advanced Photon Source (APS)
                • Allowed the scientists to ascertain the structure of these molecules as they combined to create small fibers in a liquid solution.
              • Fibers’ motion may be controlled by scientists
                • Making it possible for the fibers to interact with the spinal cells more effectively.
              • scitechdaily.com/reversing-paralysis-dancing-molecules-can-fix-spinal-cord-injuries/
              • Department of Energy (DOE) Office of Science user facility at Argonne National Laboratory. There, scientists from Northwestern University and the Air Force Research Laboratories
              • “Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury” by Z. Álvarez, A. N. Kolberg-Edelbrock, I. R. Sasselli, J. A. Ortega, R. Qiu, Z. Syrgiannis, P. A. Mirau, F. Chen, S. M. Chin, S. Weigand, E. Kiskinis and S. I. Stupp, 11 November 2021, Science. DOI: 10.1126/science.abh3602

              Dapagliphozin

              • Ki for inhibiting AChE is 25.02 µM for dapagliflozin
              • Brain concentrations are 0.5 µM and 0.3 µM,
              • Patients with Alzheimer’s disease have a reduced amount of acetylcholine neurotransmitters
                • Acetylcholinesterase inhibitors including
                  • Donepezil, rivastigmine, galantamine used to increase the acetylcholine level

              Rat model of cognitive impairment induced by scopolamine

              • Canagliflozin, similarly to galantamine, decreased AChE activity
              • Increased acetylcholine M1 receptor (M1 mAChR) and monoamines levels

              Y maze task and water maze task

              Knocking down xylosyltransferase-1 with deoxyribozyme


              Doteky

              • Probouzení a nervová soustava je silně stimulovaná doteky
              • Masáže, reflexy, hlazení...
              • Není náhoda, že na novorozeneckém oddělení se začaly nezralým novorozencům dávat hezbké oblečky z fleesu ap.

              Epigallocatechin gallate (EGCG)

              • In green tea
              • Has been shown to promote neurogenesis and protect against neurodegeneration.

              Empagliflozin

              • Ki for inhibiting AChE is 0.177 µM for empagliflozin
              • Only in the case of empagliflozin, brain concentration is enough to inhibit AChE

              Mice

              • Significantly increased cerebral BDNF (Brain-derived neurotrophic factor) levels in db/db mice
              • Improvement in cognitive functions
              • BDNF takes part in the growth, survival, and plasticity of neurons as well as in the modulation of neurotransmission.
              • Factor for the processes of learning and memorizing
              • Significant decline of BDNF was observed in patients with T2DM
                • Associated with cognitive impairment
                • Not observed in non-diabetic controls
              • BDNF is crucial
              • DMAS (Diabetes Mellitus Accelerated Atherosclerosis)
                • Had a lower expression of BDNF
                • Negatively correlated with inflammation
              • Supplementation of BDNF in mice significantly reduced atherosclerotic lesions
              • Anti-inflammatory properties of BDNF
                • Probably associated with promoting M2 macrophages polarization via STAT3
              • www.ncbi.nlm.nih.gov/pmc/articles/PMC8659196/
              • Proven to mitigate inflammation by downregulation of the JAK2/STAT1 pathway in macrophages
              • Empagliflozin after four months of treatment significantly enhanced leukocyte expression of antioxidative enzymes
                • Glutathione s-reductase
                • Glutathione catalase
                • Reduced pro-oxidative myeloperoxidase
              • www.ncbi.nlm.nih.gov/pmc/articles/PMC8659196/

              Endokrinologická kontrola ev. kompenzace

              Steroidy

              • Aby nechyběla syntéza hormonů, které jsou důležité pro neuroregeneraci
                • Steroidy
              • Function of target organs
              • testosterone
              • estrogen
                • Podobně i estrogen pro jeho schopnost stimulace neurogeneze v CNS

              Štítnice

              • Aby nebyla hypofunkce štítné žlázy
                • Také důležité pro rozvoj a funkci mozku
              • TSH
              • Free T4, free and reverse T3
                • Důležité je nemít hypofunkci štítnice pro funkci a regeneraci CNS

              Growth hormone

              • Ten bych zvažovala jako růstovou podpůrnou látku na stimulaci zhojení se a v prevenci ztráty svaloviny... asi i bez dysbalance
              • IGF-1

              FSH and LH,

              ACTH

              • Cortisol
                • Jeho zvýšené hladiny vedou ke zmenšování se hypotalamu...

              Bioidentical hormone replacement therapy

              Podpora energetického metabolismu mozku

              • Pyruvát
              • Trehaloza
              • Ribóza
              • MCT oleje - kokosový, avokádový, předmíchaná směs
              • Butyrát aj. ketolátky v kapslích

              Erytropoetin inj.

              • Mimo jiné i nervový růstový faktor
              • Lze off-label předepsat a zakoupit v injekci
                • Lze injikovat do zátylku
                • Lze nakapat do nosu - vůbec to nepálí, je to příjemný olejíček
                  • S odstupem pár dní je ostřejší čich
                    • Na zvířatech se prokázala schopnost průniku do CNS podél n. V. a n. I. vláken
                  • Může se pak objevit ucpaný nos jako rýma - vlivem asi novotvorby cév
              • Stimuluje novotvorbu cév a urychluje regeneraci nervové soustavy
                • V malé míře může stimulovat onu novotvorbu červených krvinek, ale spíše je dříve rozloží játra
              • Pokud je pacient ležící, s rizikem trombozy, tohle to může mírně zvýšit
                • Občasné podání heparinové injekce nejspíše vyváží všechna rizika
                  • Nebo alespoň dočasné v.s. alibistické podání vessel due F - perorální forma heparinu
              • Hepariny obecně nejsou špatně
                • Podporují vazbu signálních molekul na receptory
                  • Včetně těch, které jsou důležité pro novotvorbu cév a to je důležité pro hojení jakékoliv tkáně
              • Erythropoietin (EPO)
              • May play a role in neuroprotection after brain injury

              Several studies demonstrated that EPO shows

              • Antiexcitotoxic, antioxidant,
              • Antiedematous,
              • Antiinflammatory effects in TBI
              • Brain injury causes upregulation of EpoR expression

              Mice

              • Reduced number of neural progenitor cells (NPCs) and increased apoptosis has been found in the mice lacking the EPO receptor
              • EPO/EpoR signal pathway
                • Involved in neuroprotection in pathological conditions
              • Expression of the receptors for EPO
                • Significantly increased in neurons, glia, and endothelial cells after TBI
              • EPO appears to promote neuroprotection
                • Through binding to EpoR and activating JAK-2/NF-kB and PI3K signaling pathway
                  • JAK-2 phosphorylation activates PI3K/AKT and Ras/MAPK pathways
                    • And promotes STAT-5 homodimerization antiapoptotic and neurotrophic effects

              Double-blind randomized controlled clinical trial

              • EPO does not reduce the number of patients with severe neurological dysfunction
              • Effect of EPO on mortality remains uncertain in moderate or severe TBI
              • More clinical trials need to be performed to confirm the results
              • journals.sagepub.com/doi/full/10.1177/0963689717714102
              • Neukázaly se efekty v akutních stavech během krátké doby hospitalizace, ale mohly by se ukázat v delším horizontu během rehabilitace.

              Ferulic acid

              • Powerful natural antioxidant derived from plants
              • Helps speed healing by increasing glutathione levels
              • Reducing neuron death in the brain
              • Help with memory problems caused by a concussion
              ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller “Inside-Out Health,” and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science degree in human nutrition. The ACA Sports Council named him “Sports Chiropractor of the Year” in 2015. He is on the advisory board for the Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A frequently published author in peer-reviewed journals and other mainstream publications, he is a thought leader in his field and practice. His new book, “Superhighway to Health,” was published in June 2021. He can be reached at drrobertsilverman.com.

              Fingolimod

              • Medication commonly used to treat multiple sclerosis
              • Promote neurogenesis and protect against neurodegeneration in animal models.

              Fisetin

              • Flavonoid found in strawberries
              • Promote neurogenesis and protect against neurodegeneration

              Fucoxanthin

              • Neuroprotective effects
              • Nrf2-ARE and Nrf2-autophagy pathways +

              G-protein-coupled receptor agonists

              • Reduce neurogliosis in animal models.

              Ganoderma lucidum polysaccharides

              • And that they mostly focused on their roles in ischemia/reperfusion injury models. In addition, some articles on G. lucidum polysaccharides did not explore the relevant mechanisms in depth.
              • Neural Regeneration Research 17(9):p 1907-1912, September 2022. | DOI: 10.4103/1673-5374.335142

              Genistein

              • In soy, has been shown to promote neurogenesis and protect against neurodegeneration.

              Ginkgo biloba

              • Zvyšuje odolnost neuronů vůči nedokysličení a prokrvení koncových kapilár
              • Ale mohlo by to zhoršit otoky a pokles krevního tlaku - potřeba sledovat
              • Promote neurogenesis and protect against neurodegeneration in animal models

              Glucocorticoid methylprednisolone

              Glutamine

              • Non-essential amino acid,
              • Widely distributed throughout the body
              • Abundant free amino acid in circulation
              • Glutamine synthesis cannot keep up with increased requirements such as those experienced during physiological stress
              • Important for the immune response
              • Glutamine supplementation
                • Decrease infectious complications in trauma patients
              • Brain serves prominently in glutamine metabolism
                • Net producer of the amino acid
              • Brain, glutamine is involved in the glutamine-glutamate cycle
                • To conserve the carbon skeletons of neurotransmitters
                • Part of this cycle, it is synthesized from glutamate and ammonia in astrocytes
                  • Also serves as the precursor for glutamate along with alpha-ketoglurate

              Glutamate

              • Recognized as an excitotoxic neurotransmitter released after TBI
              • Patients with brain injury are also observed to experience profound hypoglutaminemia
              • Observed deficiency provides rationale for dietary supplementation
              • Nezvýší to však jen dále hladinu glutamátu ?? Nebylo by bezpečnější spíše blokovat enzym produkující glutamát z glutaminu ??

              Animal studies rat TBI model

              • Glutamine administration was shown to decrease concentrations of pro-inflammatory cytokines and apoptotic cells in gastrointestinal tissue
                • Thus reducing TBI-associated damage to gastrointestinal mucosa

              Clinical studies with glutamine and alanine dietary supplementation

              • Lower mortality rates
              • Shorter hospital lengths of stay
              • Decreased occurrences of pneumonia and stress ulcers
              • Higher lymphocyte counts in TBI patients
              • Improved immunological response
              • Future studies are needed to advance our understanding of the translational potential of glutamine as a nutritional adjuvant in TBI therapy.

              REducing Deaths due to OXidative Stress trial

              • Effect of nutritional supplementation in critically-ill patients
              • Glutamine supplementation actually resulted in increased harm and mortality in critically ill patients
              • Cautiously advocated that administration of glutamine be reserved for burn and trauma patients not in multiorgan failure
              • Much of the glutamine in that study was administered in parenteral form
              • Body of literature using enteral glutamine has shown no such outcome.
              • www.intechopen.com/chapters/46049

              Reduced glutathione (GSH), uric acid, and coenzyme Q10

              • Low molecular weight antioxidants
              • Mammals are unable to perform their synthesis
              • Depend on regular intake with diet
              • Quality of food consumed and/or supplementation is of fundamental importance
              • Link between oxidative/nitrosative damage and TBI is evident

              Glutathion

              • Injekce Tationil 600 mg 1 x až 3x denně i.m.
              • Silný antioxidant, zajímavé efekty u neurodgenerace jako Parkinsnova choroba aj.

              Glykémie

              • An increase in blood glucose
                • Common clinical symptom in patients following traumatic brain injury.
              • Death after traumatic brain injury
                • Associated with nerve injury
                • Correlated with abnormal physiological and metabolic reactions.
              • Hyperglycemia
                • Manifestation of physiological and metabolic disorders after traumatic brain injury.
                • Aggravated secondary injury to the brain.
              • Nad určitou hranici je hyperglykemie nesporně škodlivá
              • Ale na druhou stranu hypoglykemie je pro poškozené nervové buňky také smrtící
              • Není asi tedy od věci cca tušit, zda si toto tělo nemocného umí regulovat dobře
              • V případě inzulínové rezistence
                • Vyšší hladina inzulínu může blokovat syntézu ketolátek
                  • Mozek nebo jeho určitě části se mohou ocitnout v hypoglykemii
                • Sekrece inzulínu spouští i sekreci Inzulin like growth factor 1 - může fungovat jako růstový faktor
                • Inzulínová rezistence a možné testy
                  • Ranní glykemie je vyšší než je norma
                  • HOMA index (nutno stanovit hladinu inzulínu nalačno)
                  • C-peptid
              • Pokud u chronického stavu po poranění mozku chci využít výhody vylačnění a autofagocytozy
                • Budu opatrná na možný vznik hypoglykemie
                  • Delší noční lačnící pauzy bych zajistila buď suplementací přímo butyrátu a nebo dávkou MCT olejů ve večerním jídle

              Hericium erinaceus Polysaccharides


              Hericium erinaceus is an edible fungus with medicinal value that has a certain preventive effect against dementia. Hericium erinaceus polysaccharide (HEP) is a main biologically active component of H. erinaceus that exists in fruitbodies, mycelia, and culture fluids (Wang et al., 2019). HEP preconditioning induces cell differentiation, increases cell survival, inhibits ROS accumulation, blocks intracellular Ca2+ overload, and prevents mitochondrial membrane potential depolarization in glutamate-treated PC12 cells (Zhang et al., 2016). The study also found that HEP therapy ameliorates behavioral abnormalities and memory impairments in the AD mouse model. These findings indicate the great neuroprotective activities of HEP both in vivo and in vitro, which indicate it has value in the prevention and treatment of AD.
              • Neural Regeneration Research 17(9):p 1907-1912, September 2022. | DOI: 10.4103/1673-5374.335142

              Histamin bohatá strava

              • U apalického syndromu / komatu ?
              • Zvýšení histaminové aktivity na synapsích může pomoci s probuzením z komatu
                • Potraviny obsahující histamin a "budivé aminy" někdy u lidí působí urputnou nespavost
                • U apalického syndromu by mohla být naopak výhodou histamin bohatá strava

              Histaminergní metabolické dráhy

              • Activation of H3 receptor
              • Blockade of H3 receptor
                • Promotes wakefulness
              • Histamine release in the hypothalamus and other target regions
                • Highest during wakefulness
              • Histaminergic neurons display maximal activity during the state of high vigilance
                • Cease their activity during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep
              • Cerebrospinal levels of histamine
                • Reduced in diseased states where hypersomnolence is a major symptom

              Histamine deficient L-histidine decarboxylase knockout (HDC KO) mice

              • Display sleep fragmentation
              • Increased REM sleep during the light period
              • Profound wakefulness deficit at dark onset, and in novel environment
              • Similar results have been obtained when histamine neurons are lesioned
              • Histaminergic neurons of the TMN to play a critical role in the maintenance of high vigilance state during wakefulness.
              • pubmed.ncbi.nlm.nih.gov/20851648/

              Hudba

              • Hudba může pozitivně žádoucím způsobem stimulovat regenraci mozku

              Hyperforin

              • In St. John's wort
              • Promote neurogenesis and protect against neurodegeneration.

              Immunocal®

              • High cysteine
              • Important precursor from which glutathione

              2018 study by Dr Linseman’s team mouse model of TBI

              • Twice daily for 28 days prior to administration of a moderate TBI
              • Immunocal®-treated group showed a significant increase in the levels of glutathione in the brain
                • Showed less impairment in their motor and cognitive abilities than controls.
              • Mice that received Immunocal® showed less impairment in their motor and cognitive abilities than controls
              • Initial damage to the brain seemed to be similar between treatment and control groups
                • Supplemented mice had less degeneration of their neurons
                • Connections between neurons in different parts of the brain remained more intact.
              • Supplemented mice had reduced lipid peroxidation in the brain

              2014 journal Antioxidants, his group used a mouse model of ALS

              • Mutation in the gene superoxide dismutase 1 (SOD1)
              • Mice supplemented with Immunocal® had a modest delay in the age at which their symptoms presented
                • 98.5 ± 1.1 days compared to 91.6 ± 0.9 days for the untreated ALS mice
                • Mice that received Immunocal® showed less decline in grip strength (a measure of the loss of muscle control that occurs as the disease progresses)
                  • Bolstering effect on levels, both in the blood and in spinal cord tissue.

              Immunotec, Inc. (Quebec, CA) pilot clinical study in patients with mild cognitive impairment (MCI): “Nutritional Intervention With the Dietary Supplement, Immunocal® in MCI Patients: Promotion of Brain Health”. Dr Hyman Schipper at the Memory Clinic/Jewish General Hospital located in Montréal, Quebec, Canada.


              Inzulín

              • Mimo jiné taků působí jako neurotrofický růstový faktor

              Actrapid inzulín

              • Kapat do nosu - projde do CNS podél čichového nervu
                • Zvyšuje bdělost a působí jako růstový faktor
              • Sama sem si to pokusně kápnula a lehce to zaštípalo
                • Pak už sem o tom nevěděla a bylo to v pohodě
                • Může časem možná lehce dráždit k rýmě a zalhlému nosu
                • Ale tu a tam se to dá kápnout třeba do jedné nosní dírky


              Inhibitors of the Janus kinase (JAK)

              • Have been shown to reduce neurogliosis in animal models

              JAK2 inhibitors

              • Reduce neurogliosis in animal models

              JĂ­dla

              Freeze-dried papaya

              • In shaker to break down acidic foam in the stomach that causes acid reflux
              • Papaya with every meal
                • Enabled me to stop taking Nexium for acid reflux

              Little cayenne pepper

              • Strong anti-inflammatory properties.

              Ascorbic acid powder with a little KCl, papaya and cayenne

              • In roughly equal quantities

              Smoothies

              Freeze-dried maqui berries and acai berries

              Spinach, kale, and beets

              Milled sifted flaxseed powder


              The Ketogenic Diet and concussion

              • After a concussion, following a ketogenic diet
                • Can be quite beneficial for speeding recovery.
              • Ketones trigger the expression of BDNF
                • Diet offers other significant benefits in concussion
              • After a concussion, the brain’s ability to metabolize glucose is altered.
                • Providing an alternative energy source in the form of ketones has been shown to help maintain energy levels in brain cells
                  • By helping prevent ATP depletion in the mitochondria
              • Ketones help prevent neuronal cell death
              • Help quell reactive oxygen species and inflammation
              • Increase mitochondrial glutathione levels
                • By activating the Nrf2 signaling pathway
                  • Pivotal role in triggering inflammation
              • Ketogenic diet also stimulates autophagy in the brain
                • Helping to clear away cellular damage to neurons
              • Ketogenic diet effectively reduces neuroinflammation
                • By inhibiting the NF-kappaB inflammasome
                  • Inhibits pro-inflammatory cytokines TNF-alpha and COX-2
              ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller “Inside-Out Health,” and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science degree in human nutrition. The ACA Sports Council named him “Sports Chiropractor of the Year” in 2015. He is on the advisory board for the Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A frequently published author in peer-reviewed journals and other mainstream publications, he is a thought leader in his field and practice. His new book, “Superhighway to Health,” was published in June 2021. He can be reached at drrobertsilverman.com.

              Kokosový olej

              • Jednu lžíci denně - v syrovém stavu lisovaný za studena
              • Silně protizánětlivý
              • Snadno dostupná energie pro buňky
              • Antivirotický

              Preventivní CT / MRI / UZ kontroly mozku

              • Neudělala se nikde v hlavě po traumatu kapsa moku/zbytku krve?
                • Která by se zvětšovala a utlačovala by mozek ?
                • Zhoršovala prokrvení ?
              • Někdy se ukáže dodatečně s odstupem potřeba
                • Evakuace zybtků hematomu / odsátí cysty / zavedení shuntu pro hydrocefalus

              Krill oil

              Kyselina pantothenová

              NMN (nikotinamidmononukleotid)

              Ginkgo biloba

              Ženšen

              Černý pepř

              Zelený čaj

              Houby na podzim

              Kofein

              Adaptogeny

              Guarana

              Resveratrol

              Fosfatidylserin

              Bacoba Monnieri (podporuje dlouhodobou paměť) aj.

              Snížit počet jídel denně

              Zadýchat se

              Dobře spát a vyhýbat se stresům

              Omezit červené maso

              Jíst zeleninu a rostliny

              • Které prošly nějakým stresem (nedostatek vláhy, tepelný šokem, ohrožením škůdci apod.).


              Laser light application

              • Synergy among these added elements has substantially improved my clinical concussion outcomes.
              ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller “Inside-Out Health,” and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science degree in human nutrition. The ACA Sports Council named him “Sports Chiropractor of the Year” in 2015. He is on the advisory board for the Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A frequently published author in peer-reviewed journals and other mainstream publications, he is a thought leader in his field and practice. His new book, “Superhighway to Health,” was published in June 2021. He can be reached at drrobertsilverman.com.

              Lecithin

              • Stavební složka membrán a acetylcholinu

              OBTT model test:

              • nicotinamide,
              • Erythropoietin,
              • Cyclosporin A,
              • Simvastatin,
              • Levetiracetam,
              • Glibenclamide,
              • Kollidon VA64,
              • Amantadine,
              • Minocycline,
              • E64d,
              • P7C3-A20

              Levetiracetam

              • Have shown the most promise
              • Levetiracetam improved multiple outcomes in two models (FPI and CCI)
              • Lower 24-h serum levels of GFAP were associated with less hemispheric tissue loss (at 21 days after injury)
                • For a therapy that was effective (i.e., levetiracetam)
              • Has a specific effect on axonal injury or an overall benefit on neuronal death that mitigates secondary axonal loss

              Adenosine A1 receptor knockout mice

              • Develop lethal status epilepticus after CCI109

              Neuronal glutamate transporter and IL-1beta variation

              • Associations with accelerated epileptogenesis
                • Increased post-traumatic epilepsy risk
              • Regionally reduced neuronal glutamate transporter expression + sustained increases in IL-1beta levels
                • Are reversible with daily Levetiracetam treatment

              Glibenclamide

              • Demonstrated fairly robust benefit in CCI
                • But with benefit largely restricted to that model
              • Sulfonylurea-receptor 1 (Sur1)
                • Prognosticate secondary injury processes
                  • Cerebral edema and/or intracranial hypertension
              • Sur1 combined with transient receptor cation channel 4 (Trpm4) creates an octameric cation channel that is only found in the central nervous system (CNS) after injury
              • This channel is inhibited by glibenclamide
                • Promising results in both pre-clinical and clinical studies
              • Play a role in the development of brain edema and necrosis in pre-clinical models of TBI

              Kyselina alfa lipoová - Lipoic acid

              Mild TBI in rats


              Liraglutide

              • A GLP-1 receptor agonist used for treating diabetes
              • Neuroregeneration properties

              Lithium chloride

              • Treat bipolar disorder
              • Reduce neurogliosis in animal models.
              • In some natural mineral sources
              • Promote neurogenesis and protect against neurodegeneration in animal models.

              Lithium + valproát

              • Combining lithium and valproate treatment provided more beneficial effects
                • Preventing excitotoxicity of neuronal cultures
                • Improved outcome in mouse models of amyotrophic lateral sclerosis (ALS) and Huntington’s disease
                  • Than monotreatment with either drug

              Model of rat brain ischemia

              • Copriming mesenchymal stem cells (MSC) with these two mood stabilizers increased homing and migration of MSCs to the lesion site
                • Improved functional outcome


              Low doses TGF-beta

              • Shown to reduce neurogliosis in animal models.

              Liraglutide

              • GLP-1 receptor agonist used for treating diabetes
              • Potential to reduce neurogliosis in animal models

              Magnesium L-threonate

              • Helps prevent delayed brain injury and post-concussion syndrome
              • magnesium L-threonate cross the brain-blood barrier
                • More effectively than other magnesium forms
                • Don’t cause digestive upsets

              Magnesium

              Pre-clinical models

              • Shown to improve recovery following TBI

              Humans

              • One of the four key nutrients that correlated with improved somatic scores
                • When supplemented following mild TBI in humans
              • Magnesium is commonly depleted following TBI
                • Likely through interaction with transient receptor potential melastatin
                  • Leads to neuronal cell death
              • Magnesium readily enters the brain following mild TBI in rodents
                • Has not been shown to significantly increase in the CNS when supplemented in humans

              Magnesium with mannitol

              Mangan

              Myší senzorické neurony

              • The lectican CSPG aggrecan suppresses laminin-mediated growth of cultured rat sensory neurons
                • Without altering surface integrin levels by reducing levels of phosphorylated focal adhesion kinase and Src (Tan et al., 2011).
              • Activation of integrin signaling by applying manganese or an activating antibody
                • Surmounts aggrecan inhibition on elongation of cultured neurons.
              • austinpublishinggroup.com/neurological-disorders-epilepsy/fulltext/ajnde-v2-id1010.php

              Melatonin na noc

              • 5 mg a více na spaní
              • Opravdu silný liposolubilní antioxidant, který se dostává do mozkové tkáně
                • Podpora hojení kde čeho, zábrane neurodegeneracím, antivirové účinky
                • U zánětu, stresu a komatu může být jeho sekrece narušena
                • úzce souvisí s pocitem odpočatosti po vyspání se
                • Zpomaluje výrzaně stárnutí díky svým mocným regeneračním účinkům
              • Anesteziologové uvádí jako argument proč ho nepoužívat u těžce nemocných pacientů interakce s anestetiky
                • Jakmile však toto nebude hrozit a nemusíte být v umělém spánku, nevidím důvod ho nepoužít
              • Tělo v zátěži zánětem aj. snese i velké dávky kolem 200 mg / noc bez výrzanšjích nežádoucích účinků
                • Zpočáktu je po velké dávce spavost a ospalost ev. únava
                  • Ale zdaleka ne tak silná jako po barbiturátech, opiátech nebo tricyklických antidepresivech
                  • Po nějaké době užívání vymizí
                  • Mozek není utlumen a funguje výborně
                  • Na rozdíl od jiných dementogenních blbostí na spaní, toto je multietážový antioxidant a může zbaránit rozvoji degenerace a demence

              TBI patients

              • Decreased melatonin concentrations
                • Likely contributing to their sleep disturbances

              Phase I clinical trials for youth TBI to assess GABAergic effects

              • Promising
              • Be decreased even after mild TBI
              • Powerful antioxidant
              • Promote neurogenesis and protect against neurodegeneration.

              Minocycline

              • An antibiotic that also has anti-inflammatory and neuroprotective properties

              Anials

              • Reduce neurogliosis in animal models of injury and disease.
              • Antibiotic that also has neuroprotective properties
              • Promote neurogenesis and protect against neurodegeneration.

              MicroRNA-126 (miR-126)

              • Reduce neurogliosis in animal models

              Mluvení a emoce v blízkosti pacienta

              • I když pcient nebude reagovat nebo rozumět, nebo dokonce bude v komatu, přesto se může stát, že všechno to může vnímat a může tomu dokonce i rozumět, může to na něho mít velmi silný vliv
              • I zvíře,které Vám nerozumí slova, vnímá tón hlasu a atmosferu, a následně se může dostat do strachu a paniky, když se necítí v bezpečí
              • Hlasový věm stimuluje mozek v regeneraci jako každý další vstup
              • Tedy i nějaká muzikoterapie a poslouchání povídek - samozřejmě v omezeném čase (nepřehltit)
                • "Ticho léčí."
                  • Obzvláště při velké zánětlivé reakci, bolesti hlavy, snadno vzniklé únavě, vyčerpání aj.


              Matrix metalloproteinase inhibitors

              • Reduce neurogliosis in animal models.

              Exosomes from mesenchymal stem cells (MSC-exo)

              • Reduce neurogliosis in animal models.

              Myricetin

              • Flavonoid found in fruits and vegetables
              • Promote neurogenesis and protect against neurodegeneration.

              Acetyl L-carnitine

              • Energizes the brain,
              • Increases the neurotransmitter levels needed for memory, focus and learning,
              • Repairs damage to brain cells
              • Helps increase the levels and components of the neurotransmitter chemicals needed for memory, focus and learning.
              ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller “Inside-Out Health,” and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science degree in human nutrition. The ACA Sports Council named him “Sports Chiropractor of the Year” in 2015. He is on the advisory board for the Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A frequently published author in peer-reviewed journals and other mainstream publications, he is a thought leader in his field and practice. His new book, “Superhighway to Health,” was published in June 2021. He can be reached at drrobertsilverman.com.

              N-acetylcysteine (NAC)

              • Reduce neurogliosis in animal models of injury and disease

              Zahlenění plic

              • Podávání detralexu sníží cévní prosak v souvislsoti s prozánětlivým stavem a tím nadměrné zahlenění plic

              Detralex 2-0-0

              • V případě potřeby lze i navýšit na 2-2-2
              • Snižuje nejen otok nohou - žíly jsou všude
              • Jistě by se dalo dohledat, že snižuje i otoky CNS

              Bronchodilatancia

              • Mohou snížit i plicní hypersekreci hlenu a působit neuroprotektivně, muskuloprotektivně... (např. klenbuterol)

              Viregit K

              • Mohl by snížit nadměrnou produkci hlenu jako jeho běžný NÚ

              Léky na narkolepsii

              • Mohly by být i zajímavým pokusem k off-label aplikaci u vigilného komatu

              Pitolisant (a histamine H3 receptor antagonist)

              • Pitolisant has proved to be effective for both EDS and cataplexy

              Solriamfetol (a norepinephrine reuptake inhibitor)

              • Have recently been approved effective for narcolepsy in the United States and the European Union
              • Seems to have advantages in abuse potential and withdrawal syndrome

              Hydroxybutyrate preparations

              Neuronal grovth factor - NGF

              • Secreted by the target cells they innervate
                • For sympathetic neurones
              • Survival of developing neurones depend on neurotrophic factors
                • Those that fail to get enough neurotrophic factors (e.g. NGF)
                  • Die by typical programmed cell death [2]

              Neurorehabilitation

              • Rehabilitation techniques such as physical therapy, occupational therapy, and speech therapy, have been found to be helpful in promoting neuroregeneration and restoring neurological function after injury.

              NMN (nicotinamide mononucleotide)

              • Able to increase the number of mitochondria in neurons
              • Protect against aging-related neurodegeneration in animal models

              Nikotin ribosid (mononukleotide)

              • vitamín B3 v aktivní formě, vstřebatelný do CNS
              • Energetický metabolismus neuronů, podpora mitochondrií a jejich množení se
              • Lze zkusit sehnat via
                • Doc. Kaštánek (Neobotanics)
                • Hansen - brainmarket.com

              Octanol and carbenoxolone

              • Two commonly used gap junction blockers

              Needle track injury in adult male Sprague-Dawley rats

              • Octanol (710 mg/kg) or carbenoxolone (90 mg/kg)
              • Administered 30 minutes before or after
              • Two days after injury, increased cellular proliferation, activated astrocytes and microglia, and upregulation of NG2 expression were observed surrounding the injury site
              • Octanol and carbenoxolone administrated prior to injury
                • Significantly decreased cell proliferation by 60 and 70% respectively
              • Octanol
                • Administrated prior to or post injury respectively
                  • Distance of GFAP immunoreactive astrocytes from the wound margin was decreased by 32 and 18% when
                • Decreased the number of reactive microglia by 55%
                • When administrated prior to injury, octanol reduced the distance of NG2 expression from the wound by 48%.
              • Study demonstrates that two important components of reactive gliosis, cellular activation and proliferation, can be attenuated by octanol and carbenoxolone

              P7C3-A20

              • Protect neurons from death
              • Reduce neurogliosis in animal models of injury and disease

              Perilla frutescens polysaccharide


              Perilla frutescens is a traditional medicine commonly used in Southeast Asia that has therapeutic effects on many diseases. Perilla frutescens leaves, which are rich in proteins and vitamins, are highly valued for consumption and in the medical field. Polysaccharides are important bioactive components of Perilla leaves. Polysaccharide extracts isolated from P. frutescens (PEPF) exert neuroprotective effects against H2O2-induced oxidative stress in an HT22 hippocampal neuronal cell line (Byun et al., 2018). PEPF protects nerve cells against H2O2-induced oxidative damage by reducing the ROS-mediated increased intracellular Ca2+level, upregulating HO-1 protein expression, and inhibiting caspase-3. The neuroprotective effect of PEPF on HT22 hippocampal cells was achieved by activating MAPK and NF-?B and negatively regulating the PI3K/Akt pathway. Moreover, the up-regulation of Nrf2-mediated HO-1/NQO1 pathways plays important roles in the inhibitory effect of PEPF against H2O2-induced neurotoxicity. Thus, PEPF may be a promising candidate for the treatment of NDDs, and it is worthy of further investigations.

              Phenserine

              • AChE inhibitor
              • Reduce neurogliosis in animal models of Alzheimer's disease.

              Phenserine

              • AChE inhibitor
              • Promote neurogenesis
              • Protect against neurodegeneration in animal models of Alzheimer's disease.

              Small molecule inhibitors of the PI3K/Akt signaling pathway

              • Reduce neurogliosis in animal models

              Potraviny, které mají sílu

                • (max. spektrum stavebních látek a vitamínů)
              • Játra (i vitamíny rozpustné v tucích)
              • Vývary z kostí (nukleotidy aj.)
              • Mozeček z králíka aj. (další látky, které by se mohly hodit pro regeneraci mozku)
              • Vejce (žloutek - cholesterol - myelinové pochvy a oprava mozku)
              • Jablko
              • Brokolice
              • Tvaroh tu a tam

              Regenerace nervove soustavy

              • Neuroregeneration
              • Nerve re-growth
              • Regrowth or repair of nervous tissues

              Axonální růst

              • Central nervous system axons
                • Have been proven to regrow in permissive environments [1]
              • Human axon growth rates can reach
                • 1 mm/day in small nerves
                • 5 mm/day in large nerves [1]


              Inhibice neuroregenerace

              • ECT lacking laminins

              Glial scars

              • Develops rapidly
              • Primary problem to central nervous system axonal regeneration
                • Crossing or eliminating the inhibitory lesion site

              Glia

              • Produce factors inhibitors of remyelination and axon repair
                • NOGO
                • NI-35 [1]

              Zrychlená tvroba glialních jizev

              Role in the initiation of scar formation

              • Transforming growth factors B-1 and -2
              • Interleukins
              • Cytokines

              Accumulation of reactive astrocytes at the site of injury

              • Up regulation of molecules
                • Inhibitory for neurite outgrowth

              Věk

              • Axons lose the potential for growth
                • Decrease in GAP 43 expression [1]
              • Inhibitory myelin and axonal debris
                • Not cleared away as quickly [1]



              Literatura
              [1] en.wikipedia.org/wiki/Neuroregeneration


              Pregnenolone

              • Produced in the body, has been shown to promote neurogenesis and protect against neurodegeneration.

              Prevence prochladnutí nohou

              Pro-resolving mediators

              • Reducing inflammation in the brain from a concussion is extremely important
                • For avoiding long-term tissue damage.
              • Supplements of special pro-resolving mediators promote the natural termination of the inflammation process
                • By counteracting the damage from inflammatory cytokines
                • Decreasing TNF-alpha and IL-6 synthesis
                • Increasing anti-inflammatory IL-10 synthesis
              ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller “Inside-Out Health,” and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science degree in human nutrition. The ACA Sports Council named him “Sports Chiropractor of the Year” in 2015. He is on the advisory board for the Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A frequently published author in peer-reviewed journals and other mainstream publications, he is a thought leader in his field and practice. His new book, “Superhighway to Health,” was published in June 2021. He can be reached at drrobertsilverman.com.

              Progesterone

              • Neuroprotective effects in patients exposed to TBI


              Vyprazdňování

              • Pokud je obtíž s obstipací, rozhodně bych volila prostředky, které nedráždí střevo a neodvodňují člověka
              • S výhodou je použít látky, které stimulují protizánětlivou střevní mikrofloru - G+ bakterie a produkci antioxidačních metabolitů
              • Jako vhodná se mi jeví:

              Laktulóza

              Psylium

              • Jako vláknina vlivem fermentace uvolní cca až 50% butyrátu a nikoliv nadbytek k. propionové jako většina ostatních vláknin
              • Kyselina propionová může podporovat stav narkozy a zhoršeného probouzení (zachyceno v jednom článku, nutno dále dohledat)

              Prokrvení mozku

              • Bez polštáře - za předpokladu, že nehrozí reflux a že není zvýšený intrakraniální tlak
              • Regulace intrakraniálního tlaku

              Raising the head of a traumatic brain-injured individual

              • Generally has rapid effects.
              • ICP is reduced by displacement of CSF from the intracranial compartment

              Proteiny ve stravě v adekvátní dávce

              • Prevence kachexie a proleženin, ztráty svaloviny
              • 1-1,5g/kg hmotnosti

              Quercetin

              • Promote neurogenesis and protect against neurodegeneration.
              • Anti-inflammatory properties
              • Reduce neurogliosis in animal models

              Resveratrol

              • Anti-inflammatory properties
              • Reduce neurogliosis in animal models

              EGCG (epigallocatechin gallate)

              • Anti-inflammatory properties
              • Reduce neurogliosis in animal models


              rTMS and amantadine

              rTMS

              2 double-blind placebo-controlled randomized clinical trials

              • Different types of rTMS
              • Effects of our previously published rTMS protocol - persons remaining in states of disordered consciousness after TBI
              • Effects of a type of rTMS, intermittent theta burst stimulation, on attention impairments persisting after mild TBI

              Rapamycin

              • Immunosuppressant drug
              • Reduce neurogliosis in animal models of injury and disease
              • Promote neurogenesis and protect against neurodegeneration in animal models.

              Rapastinel (GLYX-13)

              • An NMDA receptor modulator
              • Promising results in animal models
              • Possible treatment for various neurological disorders such as depression and PTSD.

              Reflux žaludku

              • Je přítomen - nehrozí plícím ?
              • Je nutné polohovat pacienta ?
              • Není potřeba upravit dávky jídla do žaludku ?
              • PH metrie ?
              • Enterosgel jako zátka na konec jídla ?
              • Ps: léky na snížení kyselosti žaludeční šťávy jsou riziko pro snažší vznik pneumonie a SIBO
              • Smí si lehnout na záda bez polštáře, aby se více prokrvil mozek ?
                • Lze takto spát aniž by se zakuckala žaludeční šťávou refluxem ?

              Riluzole

              • Used to treat Amyotrophic Lateral Sclerosis (ALS)
              • Reduce neurogliosis in animal models.
              • Also have been studied for its neuroregeneration properties.

              Robot assisted therapy

              • Work by way of neuroplasticity [1]

              Rolipram

              • A phosphodiesterase 4 (PDE4) inhibitor
              • Promote neurogenesis and protect against neurodegeneration in animal models.

              Growth factor therapies

              • Such as nerve growth factor (NGF),
              • Brain-derived neurotrophic factor (BDNF)
              • Glial-derived neurotrophic factor (GDNF)
              • Studied as potential therapies for
                • Promoting neuroregeneration
                • Restoring neurological function after injury

              Růstový hormon

              • Po TBI může dojít k deficitu růstového hormonu
              • Je s otázkou, zda je jeho podání výhoda pro neuroregeneraci
              • Je dostupný, teoreticky by mohl pomoct v hojení CNS
              • Teoretické riziko:
                • Stimulace růstu celého těla/jiných tkání
                  • Konzumpce cenných živin, které pak chybí pro regeneraci CNS
              • Otázka: intranazální podání - dostane se podél vláken n.V. a n. I. do CNS
                • Mělo by smysl ?

              Selenium

              SGLR-2-inhibitory

              • Neuroprotective potential
              • Lipid-soluble
              • Reach the brain/serum ratio from 0.3 to 0.5
              • SGLT receptors are present in the central nervous system (CNS)

              SGLT2i

              • Anti-inflammatory and anti-atherosclerotic effect
              • Reduction of proinflammatory cytokines, M2 macrophage polarization, JAK2/STAT1 and NLRP3 inflammasome inhibition
              • Mitigate oxidative stress
              • SGLT2i improve endothelial function
                • Prevent remodeling
              • Protective effect on the neurovascular unit, blood-brain barrier, pericytes, astrocytes, microglia, and oligodendrocytes

              Flozins

              • Not fully SGLT2-selective
              • Affinity for the SGLT1 receptor
                • Associated with protection against ischemia/reperfusion brain damage
              • Flozins are also able to inhibit AChE
                • Contributes to cognitive improvement
              • Theoretically, to obtain the neuroprotective effect associated with SGLT1 inhibition in diabetic patients
                • Sotagliflozin and Canagliflozin
                  • Should be preferred over Dapagliflozin, Empagliflozin, and Ertugliflozin

              Empagliflozin

              • Significantly increases the level of cerebral BDNF
                • Modulates neurotransmission
                • Ensures growth, survival, and plasticity of neurons
              • May be able to restore the circadian rhythm of mTOR activation
              • SGLT2i have a great potential to protect against atherosclerosis and cognitive impairment in patients with type 2 diabetes mellitus
              • www.ncbi.nlm.nih.gov/pmc/articles/PMC8659196/

              Sirtuins activators, like Resveratrol

              • Increase the activity of sirtuins enzymes that regulate the lifespan of cells, this process has been shown to be involved in neuroregeneration.

              Spánková apnoe

              • Nedusí se v noci ? Jaké má pauzy ?
              • Chrápe ?
              • Noční hypoxie by mohla zhoršovat schopnost regenerace...

              Signal transducer and activator of transcription (STAT) pathways

              • Have been shown to reduce neurogliosis in animal models

              Stilnox

              Vzbuzení pacientky z komatu na pár hodin

              Suramin

              • Polysulfonated naphthylurea
              • Synthesized and designed as a treatment for trypanosomiasis and selected malignancies and metastatic diseases
              • Interfering with many other pathophysiological processes in animal models
              • Enhance renal regeneration after ischemia/reperfusion injury
              • Attenuate liver damage following CD95 stimulation and endotoxic shock
              • Reduce brain injury induced by ischemia
              • Suppress myocardial inflammation
              • Anti-fibrotic effect in liver and muscle
              • Inhibits apoptosis
              • Suppresses expression of proinflammatory cytokines
              • Inactivates myofibroblasts
              • Stimulates proliferation of renal epithelial cells
              • Antifibrotic effects of suramin in injured skeletal muscle after laceration.
              • Suramin inhibits death receptor-induced apoptosis in vitro and fulminant apoptotic liver damage in mice.
              • Suramin: potential in acute liver failure.
              • The effect of suramin on inhibiting fibroblast proliferation and preventing epidural fibrosis after laminectomy in rats.
              • Suramin inhibits Hsp104 ATPase and disaggregase activity.
              • Suramin inhibits the development and progression of peritoneal fibrosis.
              • Suramin disrupts the gliotic response following a stab wound injury to the adult rat brain.

              Rat

              • Suramin, a polysulfonated napthylurea
              • Inhibit the binding of many different cytokines to their cell surface receptors
              • A single dose of suramin (5 ul, 75uM) or saline vehicle was injected intracerebrally
                • Through the same needle used to make the stab wound at the time of lesioning
              • Suramin-treated animals showed an obvious reduction in several parameters of CNS inflammation:
                • Cellular proliferation, GFAP levels, and tenascin-C immunoreactivity
                  • Reduced in suramin-treated
              • GFAP immunoreactivity was strikingly reduced at 3 days after injury
                • Transient
                • Less apparent at 7 days
                • Disappeared by 30 days after injury
              • Tenascin immunoreactivity was significantly diminished at 24 h in suramin-treated lesion areas,
              • Suramin can antagonize tenascin expression by cultured astrocytes treated with bFGF
              • Disruption of the fiber tract within the lesion site
                • Suramin-treated animals displayed numerous fibers spanning the lesion
              • Single injection of suramin transiently inhibits the gliotic response
                • May be sufficient to ameliorate subsequent tissue damage
              • link.springer.com/article/10.1023/A:1006995624754

              Jak je na tom sympatikus/parasympatikus

              • Stabilita krveního tlaku, tepu srdce ?
              • Pohotovost k bronchokonstrikci ? astmatu ?
              • Ke zvážení by byly medikamenty z terapie Parkinsnovy choroby
                • Amantadin - Viregyt K - u některých lidí pomohl k probuzení se
              • Ke zvážení by byly i další neuroprotektivní dopaminergní medikamenty
                • Jen jde o to, aby při dysregulaci parasympaticku/sympatiku nevznikla
                  • Hypertenzní krize
                  • Maligní srdeční arytmie
                  • Bronchospasmus


              Telomerase activators such as TA-65

              • Derived from the Chinese herb Astragalus
              • Promote neurogenesis and protect against neurodegeneration in animal models
                • By extending telomeres.

              Taurine

              • Is an essential supplement for a complex and compelling reason
              • Glutamate enters neurons via a receptor called NMDA (N-methyl-D-aspartate)
              • Normally, NMDA receptors let controlled amounts of glutamate into the neurons
                • Excites them and activates the brain’s areas related to learning and memory
              • Concussion injures neurons release large amounts of glutamate
                • Glutamate excites the neurons too much (excitotoxicity)
                • Leads to impaired function and even neuron death
              • Restore the ability to form new pathways between neurons
                • Need to block the excess glutamate
              • taurine protects neurons from glutamate-induced neuronal toxicity
              • www.chiroeco.com/concussion-treatment-supplements/

              <2>Taxol

              Inhibice tgf-beta


              Theanin

              • Zvyšuje produkci GABA, ale při časté konzumaci / vyšší dávce může u lidí vyvolat úzkost a strach
              www.brainline.org/video/not-all-nutritional-supplements-are-safe-after-brain-injury

              Tibolone

              • The Synthetic Steroid
              • Decreases Reactive Gliosis and Neuronal Death
                • In the Cerebral Cortex of Female Mice After a Stab Wound Injury.
              • Mol Neurobiol. 2018 Nov;55(11):8651-8667. doi: 10.1007/s12035-018-1008-x. Epub 2018 Mar 26. PMID: 29582398

              Thymoquinone

              • In Nigella sativa (black seed)
              • Promote neurogenesis and protect against neurodegeneration.

              Ursolic acid

              • Many fruits and herbs
              • Promote neurogenesis and protect against neurodegeneration.

              Vhodné podmínky pro regeneraci mozku

              • Po poranění je potřeba regenerace stejně jako při neurodegeneraci
              • Neváhala bych použít poznatky Dr. Daleho Brednesna z terapie Alzheimerovy choroby z programu RECODE
                • Viz obrázky dole z knihy: Nepodliehajme Alzheimeru


              Virtual reality therapy

              • Vizualizace pohybu, který v daný moment není vhodný
                • Stimuluje regeneraci a přeuspořádání mozku, aby vhodný byl

              Vitamín D

              • Je to mocný nerový růstový faktor

              Vigantol olejíček

              • Lze kapat do nosu - nosem se vtřebá část podél čichového nervu do mozku, kde může působit
                • 1 kapka je cca 400 IU
                • Za den klidně až 2000 IU = do každé nosní dírky jednu kapku 2x denně

              Infadolan mast

              • Koncentrát vitamínu D a A
                • Mazat nohy či jiné části těla, aby se vstřebal a stimuloval nervy k životu
              • Ideálně i v místě nervové léze (v obalsti zad aj.)

              Kolik vitamínu D je v krvi ?

              • Aby nebyl nedostatek !!! (i zdraví lidé, co chodí pravidelně ven trpí většinu roku deficitem !!!)
                • Riziko deficitu vitamínu D vzrůstá s hospitalizací, immobilitou, malnutricí a s věkem !!!
                • Nedostatek vede k zrychlenému odvápnění kostí, které se děje i tak při inaktivitě !!!
              • Nedostatek vitamínu D zhorší funkci nervové i svalové soustavy !!!
              • Nepodávala bych žádné velké dávky vápníku ve stravě
                • Obava o ledviny uležících pacientů = nutnost dostatečného pitného režimu
                • Hyperexictace neuronální při dysregulaci vápníku intracelulárně

              Vitamín K

              • Podání vitamínu D je potřeba spojit s podáváním Vitamínu K !!!
                • Pomůže vychytávat vápník zpět do kosti, zmírní intracelulární dysregulaci vápníku (snad)
                • Ale pozor, může zvýšit koagulaci krve
              • Toto je vhodné snížit dostatečným příjmem rybího tuku, který koagulaci zase mírně snižuje

              Hořčík, zinek, křemík, bór...

              • Spolu s podáním vitamínu D p.o. je dobré současně vždy podati nějaké minerálie
                • Aby se zvýšeně nevstřebávala jenom kontaminace typu Al, As, Pb, Hg,...

              Vitamíny řady B

              • Nezbytné kofaktory pro buněčné množení a regeneraci jakékoliv tkáně, především nervové
              • Vitamíny řady B v aktivní podobě:
                • B6
                • B12
                • B9
                • B1 (samotný deficit thiaminu může vyvolat zmatenost až komatosní stav)
              • K tomu všemu bych podala vit. B12 v injekcích - zpočátku obden, pak jednou týdně


              Vitamíny řady B


              Zinc

              • Cofactor of superoxide dismutase
              • Has shown promise as a supplement to TBI therapy

              Animals

              • Reduce inflammation, apoptosis, and autophagy in pre-clinical models of neural injury

              Rats following TBI

              • Zinc supplementation (180 ppm) for four weeks was also shown to
                • Decrease depression and anxiety in rats following TBI

              Lidé

              • Hypozincemia has been linked to depression
                • Could be correlated to the incidence of depression after TBI
              • Zinc serum levels are reduced in mild TBI patients
                • Possibly due to the hypoalbuminemia that can develop after injury
                • Can disrupt serum zinc availability

              Sleep

              • Essential for neuroregeneration
              • Brain consolidates memories and repairs itself.

              Stress Management

              • Chronic stress has been shown to impair neuroregeneration
              • Manage stress through techniques such as meditation, yoga, or therapy can be beneficial.

              Avoiding toxins

              • Exposure to toxins such as heavy metals, pesticides, and pollution can impair neuroregeneration, so reducing exposure to these toxins as much as possible is important.

              Socialization

              • Studies have found that socialization and a good social support can have a positive impact on neuroregeneration

              Mental stimulation

              • Engaging in activities that challenge the mind, such as puzzles, learning a new language or skill, have been shown to have positive effects on the brain and promote neuroregeneration.

              Rehabilitation

              • Physical therapy, speech therapy and other forms of rehabilitation can help the brain and body to re-learn to function after an injury or disease.

              Avoid smoking and excessive alcohol consumption

              • These can have a negative impact on the brain's ability to repair and regenerate itself
O úroveň výše

Poslední aktualizace: 4. 3. 2024 20:57:09