MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Neurotrauma - něco to dělalo - KLINICKY

Activity-based therapy

  • (also known as activity-based restorative therapy, or ABRT) is an aggressive exercise-based therapy that aims to improve sensory perception and muscle function in a patient’s body below their level of injury. When you engage in this type of therapy, you are physically taken through a series of everyday movements — all while your entire body is out of your wheelchair — that involves strength training and load-bearing exercises.
  • These spinal cord injury exercises involve repeated movements, which aim to help you to establish functional movement patterns that:
Promote neuroplasticity;

Improve range of motion (ROM) and flexibility;

Develop core and trunk strength;

Create load-bearing capabilities;

Improve bowel regularity; and

Promote bone health.

Studies show that engaging in weight-bearing activities “have not only been shown to slow the loss of bone during the acute stage of SCI and decrease extensor muscle spasms, but also to provide a wide range of benefits imperative to overall health.”

Enzogenol

Small pilot clinical trial, 60 patients after mild TBI, symptoms 3 - 12 months after injury

  • Oral enzogenol (1 g/die) for 6 weeks
  • Assessed at baseline, 6, 12, and 16 weeks.
  • Patients receiving enzogenol were found to have significantly
    • Fewer self-reported cognitive failures than those in the placebo group

TBI patients in a randomized, controlled study

Lactobacillus rhamnosus a Bifidobacterium lactis Bb12

Pregnenolone (PREG)

  • Enhances learning and memory

Rhodents

  • Increases myelination in rodent models
  • Decreases in PREG have been associated with depressive symptoms
  • PREG is also metabolized to Allopregnanolone (ALLO)
    • An anxiolytic downstream NS
    • Enhances neurogenesis in rodents

Treatment with PREG in OEF/OIF era Veterans with mild TBI

Thymosin beta 4


VX-210 - Rho inhibitor C3

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.

Zolpidem/Ambien


BalanceOil se změřením omega 3 indexu



Branched-chain amino acids (BCAAs)

  • Essential amino acids
  • Valine, isoleucine, and leucine
  • Regulating protein synthesis, gluconeogenesis, and energy metabolism
  • Major source of nitrogen for producing glutamine in the brain
  • Catabolism of excess BCAAs
    • Branched-chain aminotransferase isoenzymes, mitochondrial BCATm and cytosolic BCATc
    • Resulting product of this process is glutamate
      • Major excitatory neurotransmitter
      • Precursor of alpha-ketoglutarate
  • Irreversible step in BCAA catabolism is catalyzed by the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKDC) enzyme complex
  • BCKDC catalyzes oxidative decarboxylation of the BCKA products of the BCAT reaction
    • Forming NADH and the respective branched-chain acyl CoA derivative of each BCAA.
  • www.intechopen.com/chapters/46049

Brain injured mice or sham-injured mice

  • Consumed water or water containing BCAAs
  • Overall cognitive improvement with a simultaneous restoration in net synaptic efcacy
  • Dietary delivery of BCAAs
    • Ameliorates hippocampal-dependent cognitive dysfunction
    • Better restoration of net synaptic efcacy after concussive brain injury
  • In every animal, cognitive improvement occurred only in conjunction with restored net synaptic efcacy.
  • www.intechopen.com/chapters/46049

Clinical meassurments

  • Levels of all three BCAAs in patients with mild TBI relative to healthy volunteers is decreased.
  • BCAA levels are further reduced in patients with severe TBI compared with all groups.
  • www.intechopen.com/chapters/46049

Short-term intravenous supplementation of BCAAs in rehabilitation patients with TBI

  • Enhances recovery of cognitive function,
  • Induces a supraphysiologic plasma content of BCAAs
  • Increases tyrosine plasma concentration.
  • Plasma amino acid levels remained decreased in the posttraumatic rehabilitation phase (1-22 months).
  • 40 patients with TBI were randomly assigned either intravenous BCAAs or placebo.
  • Plasma tyrosine concentration improved in the group given BCAA supplementation
  • Overall disability improvement was greater than that noted in the placebo group.
  • Supplementation of BCAAs in TBI restores plasma levels to the normal range without having a negative effect on levels of precursors of brain catecholamines and serotonin.
  • www.intechopen.com/chapters/46049

Another study revealed that BCAA supplementation

  • May aid in recovery from a posttraumatic vegetative or minimally conscious state, thus reducing the risk of the vegetative state persisting over time.
  • By Aquilani et al., supplemented patients for 15 days by intravenous route with either BCAAs or placebo who were either in a posttraumatic vegetative or minimally conscious states.
  • The 15-day period of these trials is too short to draw any meaningful conclusions regarding that adaptation of BCAAs.
  • www.intechopen.com/chapters/46049

Elevated plasma phenylalanine

  • Was associated with decreased ICP and increased jugular venous oxygen saturation (SjvO2)

Higher plasma isoleucine and leucine levels

  • Were associated with increased ICP

Higher plasma leucine and valine

  • Were linked to decreased SjvO2
  • www.intechopen.com/chapters/46049
  • Therefore hyperalimentation with enteral nutrition should be carefully performed to avoid harmful side effects of amino acids while promoting improvements in brain metabolism.

Brain exercises

  • May be as useful as drugs to treat diseases as severe as schizophrenia
  • Plasticity exists from cradle to the grave
  • Radical improvements in cognitive functioning are possible even in the elderly
    • How we learn, think, perceive, and remember [1]
      • Michael Merzenich

Constraint-induced movement therapy

Functional electrical stimulation

Treadmill training with body-weight support


Coordination dynamic therapy

  • To 18 patients (average age 31 years) after a spinal cord injury between C4/5 and L4/5;
  • The therapy was administered on average 5 years after the injury
    • For a minimum of 3 months.
  • All complete spinal cord lesions became incomplete
    • I.e. motor functions improved below the lesion level
    • Including trunk stability and arm, hand and leg functions.
  • The organization of the CNS, quantified by the coordination dynamics between arm and leg movements, improved
    • By 42% for forward and
    • By 49% for backward moving
    • When exercising on a special coordination dynamic therapy device.
  • Improvements of the coordination dynamics were 53%, 32% and 48% for lesions in the cervical, thoracic, and lumbar range, respectively.
  • The plasticity for spinal cord lesions was thus higher when the intumescence was lesioned.
  • Since the coordination dynamics did not change substantially prior to coordination dynamic therapy, did further improve with continued therapy, and worsened when the therapy was terminated, it is concluded that the improvement of CNS functioning above and below the spinal cord lesion level was due to the therapy.
  • Since in stroke and traumatic brain lesion the CNS functioning further improved if the therapy was continued over longer time periods beyond 3 months, it is suggested that spinal cord lesions can partly be cured if coordination dynamic therapy is administered for 1 to 2 years.
  • pubmed.ncbi.nlm.nih.gov/12224474/

Creatine

  • Frequently used to increase strength and muscle mass
  • Creatine metabolism plays a key role in ATP turnover in the metabolically active brain.
  • Cerebral creatine levels have been observed to decrease after TBI

Studies

  • Significant neuroprotection against oxidative stress and ischemia

TBI therapy have been limited to animal models

  • Creatine as a nutritional component
  • Much potential exists for clinical research to further define its translational relevance.
  • Creatine-induced neuroprotection
    • Related to its effects on mitochondrial bioenergetics
    • Binding to mitochondrial creatine kinase (CK)
      • To exert structural protection allowing the enzyme to maintain its ability to inhibit free radical generation.
  • Creatine supplementation
    • Lowers mitochondrial membrane potentials
    • Reduces mitochondrial levels of reactive oxygen species (ROS) and calcium
    • Maintaining the levels of adenosine triphosphate (ATP)
  • Effects result in inhibition of mitochondrial permeability and reduced neuronal loss.
  • www.intechopen.com/chapters/46049

Creatine

  • In the brain, creatine has powerful neuroprotective effects.
  • Levels decrease after a concussion.
  • Raising them with supplements helps prevent brain damage following traumatic brain injury by preserving function in the mitochondria and increasing energy production in neurons.
  • Supplemental creatine provides immediate energy to heal brain cells.
  • Creatine also improves cognition
  • Significantly decreases headaches, dizziness and fatigue after 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.

Hybrid hydrophobic derivatives of creatine, creatinyl amino acids

  • Synthesized with the aim to establish better penetration across the blood-brain barrier.

In vivo

  • Maintain both their neuroprotective abilities and chemical stability.

Animal studies mouse and rat TBI models

  • Chronic supplementation of creatine
    • Decrease the extent of cortical damage by as much as 36% and 50%, respectively
  • Compared to rats receiving a control diet
    • Rats fed a creatine-enriched diet have also shown decreased levels of neurochemical markers of TBI-induced acute cellular injury.
  • Dose-dependent manner and cumulatively provide promising preclinical data to steer pilot clinical studies
  • www.intechopen.com/chapters/46049

Creatine

  • Most commonly taken by weight-lifters to increase muscle mass
  • May also have neuroprotective effects that aid in TBI treatment

Creatine in two human-based studies in children with moderate-severe brain injury


Curcumin

  • In the spice turmeric, curcumin is a vital supplement for treating concussion.
  • Curcumin passes through the blood-brain barrier
  • Powerful antioxidant and anti-inflammatory effects
  • After a traumatic brain injury, curcumin supplements can help
    • Reduce cognitive impairment
    • Stabilize energy use in the brain
    • Reduce membrane damage in the neurons

In animal studies and in small human trials

  • Supplement raises BDNF production
  • Curcumin also increases blood flow to the brain
  • Protects brain cells against free radical damage
  • Supports anti-inflammatory pathways and enhances DHA’s bioavailability
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.

Animals exposed to TBI

  • Curcumin reduce neurogliosis in animal models of injury and disease.
  • Shown to promote neurogenesis and neuroplasticity.

Electrical stimulation

  • Electric currents that mimic brain signals to stimulate areas below the level of injury.
This study shows that a combination of intensive physical training and epidural electrical stimulation can improve motor functions in individuals with motor complete injuries. Additionally, all 4 participants started the study at least 2.5 years after their spinal cord injuries (proving that recovery is not limited to a certain amount of time).

Exoskeletons


One option that is currently available to help individuals with spinal cord injuries get on their feet again is wearing an exoskeleton.
Exoskeletons are wearable robotics that use sensors and momentum to facilitate movements. This is ideal for individuals with severe or complete spinal cord injuries. It allows them to get on their feet and move around, which helps promote circulation, reduce muscle atrophy, maintain bone density, and decrease the risk of developing pressure sores.

Functional electric stimulation (FES)

  • Computer and electrodes to stimulate paralyzed muscles through small bursts of energy have shown promising results. Through this stimulation, patients have demonstrated improvements in their respiration, bladder and bowel control, and hand movements. Some patients have even been able to move their legs for the first time in years.
  • Although the FES leg cycling exercise on its own may be insufficient to promote aerobic fitness, studies have shown that “combined arm + leg FES training at submaximal exercise intensities may lead to greater gains of aerobic fitness than would arm exercise alone.”
  • If you’ve suffered a traumatic injury to your C6 cervical spinal cord, the best thing that you can do is seek treatment as early as possible. Once you’re able to do so, begin engaging in physical therapy, activity-based therapy, and exercises to keep your body moving. Although this will be challenging, it will only serve to your benefit.
  • www.spinalcord.com/blog/c6-spinal-cord-injury-healing-and-exercises

Glutamine + probiotic

TBI, enteral nutrition enriched with antioxidants and neuromodulatory agents

  • no mortality differences
  • Glutamine/probiotic group demonstrated
    • Lower infection rates and infections per patient
    • Shorter intensive care stays
    • Fewer ventilator days
  • www.intechopen.com/chapters/46049

Glycerophosphocholine (GPC)

  • Used to prevent damage to brain cells after blood flow - and thus oxygen - has been cut off
  • Supports the brain's ability to recover after traumatic brain injuries
  • Helps to reduce the symptoms associated with concussion and post-concussion syndrome
  • Form of choline that has been shown to protect and repair damaged brain cells

Study on GPC twenty-three patients who suffered from concussions and cerebral contusions

  • Given GPC for a 3 month period
  • At the end of the study ninety-six percent of the patients' mental faculties had improved significantly
  • blog.designsforhealth.com/node/91

Human echolocation

  • Learned ability for humans to sense their environment from echoes
  • Used by some blind people to navigate their environment
    • Sense their surroundings in detail
  • Studies in 2010 and 2011 using functional magnetic resonance imaging
    • Parts of the brain associated with visual processing are adapted for the new skill of echolocation
  • Click-echoes heard by these patients
    • Processed by brain regions devoted to vision rather than audition [1]

Indomethacin

  • no suxcess of clinical trials up to now
    • Due to the heterogeneity of TBI
    • Ongoing trials have grouped patients into more distinct categories, and may found better results for select subgroups of TBI.
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC5491366/

Lithium

  • GSK-3beta inhibitors
  • 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)

Magnesium

  • Essential for maintenance of vital cellular function
  • Including glycolysis,
  • Membrane structure and function,
  • protein synthesis
  • DNA replication.
  • Magnesium also plays an important role in central nervous system following injury
  • After TBI, the normal homeostatic mechanisms of magnesium are deranged
    • Rapid decline in magnesium levels in the brain.
    • Disruption of normal magnesium homeostasis has actually been shown to correlate with the severity of neurologically-mediated behavioral deficits following injury
  • magnesium pharmacotherapy may aid in the treatment of various CNS injuries
    • Including ischemia and cortical lesions
    • Effective in some of these arenas
  • Manipulation of dietary magnesium may have an impact on the recovery of function following TBI.
  • Regulation of key pathways involved in the delayed secondary phase of brain injury
  • magnesium is a noncompetitive inhibitor of the NMDA receptors
  • Following acute brain injury
    • Tissue magnesium is depleted
      • Loss of homeostatic control of the NMDA receptors
      • Massive influx of calcium leads to neuronal degeneration and cell death

Animal studies

  • Dietary magnesium deficiency prior to injury
    • Worsens recovery of function
  • Systemic administration of magnesium pre- or post-injury
    • Significantly improves functional recovery

Studies in rats

  • magnesium after brain injury did offer neuroprotection
  • Bareyre et al. - beneficial effects on behavioral outcomes
  • Attenuated cortical histological damage
  • Magnesium therapy administered up to 24 hours after injury in rats
    • Significantly improved motor outcome and behavioral parameters in rats with severe diffuse traumatic axonal brain injury
  • magnesium supplementation
    • Reduce long-term motor and cognitive deficits after TBI in rats
      • May result in decreased post-traumatic stress and anxiety

Clinical studies

  • Disruption of magnesium homeostasis has been observed in human traumatic brain injury.
  • Clinical studies in TBI patients have failed to show a consistent clinical benefit
  • Continuous infusions of magnesium for 5 days given to patients within 8 hours of moderate or severe TBI
    • Were not neuroprotective
    • May even have a negative effect in the treatment of significant head injury

Prospective clinical trial by Dhandapani et al.

  • magnesium sulfate administered to TBI patients within 12 hours of their injuries
  • Produced decreased mortality
  • Improved neurologic patient outcome

Number of studies looking at the role of magnesium supplementation in combination with other

  • Hypothermia and hyperoxia - with varied results in both preclinical and clinical trials

Meta-analysis of all randomized controlled trials


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]


Synaptic plasticity

  • Ability of the brain to change throughout an individual's life, e.g., brain activity
    • Associated with a given function can be transferred to a different location
    • Proportion of grey matter can change
    • Synapses may strengthen or weaken over time [1]
  • Active, experience-dependent re-organization of the synaptic networks of the brain
  • Involving multiple inter-related structures including the cerebral cortex
  • The way experience can influence the synaptic organization of the brain

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

Nutritional intake

  • None of the patients met the recommended daily allowance for all 14 specified nutrients
  • Worsened outcome scores were linked with the lowest nutrient intake compared to those who had the highest
  • TBI patients who were malnourished at the time of admission
    • Exhibited lower albumin and prealbumin levels
    • Correlated to have poor neurological scores
  • Nutritional supplementation can improve outcomes following mild TBI.
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC5491366/

Omega-3 fatty acids

The Effects of Fish Oil Supplementation on the Brain Health of Collegiate Football Athletes ClinicalTrials.gov Identifier: NCT04796207

  • Dohledat výsledky studie, byla dokončena 2021
  • Randomized, double-blind, placebo controlled trial
  • 3.0 grams of docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) - DHA and EPA (2:1 weight ratio)
      • 6 capsules preferably with breakfasts 3 times a week
    • Can reduce blood biomarkers of sub-concussion injuries compared to placebo (high-oleic safflower oil) over a course of the American football season among collegiate football athletes ?
  • clinicaltrials.gov/ct2/show/NCT04796207?type=Intr&cond=Brain+Injuries%2C+Traumatic&draw=7&rank=547

OPTIMA-TBI Pilot Study (OPTIMA)

  • Fish Oil 1000 mg (contains 500 mg DHA & 100 mg EPA)) or placebo capsules

Neuroinflammation

  • One of the recognized mechanisms of secondary brain injury
  • In response to primary brain injury
  • Activated microglia and injured neurons both release signaling proteins
    • Cytokines and chemokines

Omega-3 and omega-6 fatty acids

  • Major components of immune cells and neuronal cell membranes
  • Precursors to neuromodulatory lipids such as
    • Eicodanoids,
    • Endovanilloids
    • Endocannabinoids
  • Have antinociceptive and anxiolytic properties

Docosahexaenoic acid (DHA)

  • One of the most abundant fatty acid components of brain cell membrane phospholipids

Rodent model studies

  • Dietary supplementation with omega-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA])
    • Decreased secondary axonal injury
    • Attenuated endoplasmic reticulum stress response
    • Decreased neuroinflammation post-TBI
    • Improved short and long-term neurologic outcomes
  • DHA supplementation post-TBI
    • Enhances neurogenesis by counteracting reductions in neuroplasticity biomarkers such as
      • Brain-derived neurotrophic factor
  • DHA deficient rodents
    • Are more likely to have a greater amount of axonal injury
    • Slower recovery neurologic recovery post-TBI

Study of collegiate football players

Omega-3 fatty acids

  • Reduce neurogliosis in animal models of injury and disease.
  • Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
    • Omega-3 fatty acids found in fish oil
    • Promote neuroregeneration and protect against neurodegeneration.

Overtake of function

  • People recovering from stroke
    • Support for neuroplasticity
      • Regions of the brain remained healthy could sometimes take over, at least in part, functions that had been destroyed [1]

Progesterone

  • Dr. Donald Stein and Dr. David Wright
    • First treatment in 40 years that has significant results in treating traumatic brain injuries
      • no known side effects
      • Being cheap to administer
  • Female mice seemed to recover from brain injuries better
    • Than male mice
    • At certain points in the estrus cycle
  • Different levels of progesterone
    • Higher levels of progesterone
      • Faster recovery from brain injury in mice [1]
  • Clinical trials
    • Progesterone offers no significant benefit for traumatic brain injury human patients [1]

Progesterone injections

  • In brain-injured patients after
    • Traumatic brain injury (TBI)
    • Stroke
  • Reduces
    • Edema
    • Inflammation
    • Neuronal cell death
  • Enhances
    • Spatial reference memory
    • Sensory motor recovery
  • Clinical trial, a group of severely injured patients
    • 60% reduction in mortality after three days of progesterone injections [1]
  • Multi-center NIH-funded phase III clinical trial of 882 patients
    • Treatment of acute traumatic brain injury with progesterone
      • Provides no significant benefit to patients when compared with placebo [1]

Rehabilitace

  • Prevence zatuhnutí kloubů
  • Protahování zkracujících se svalů a šlach, aby nedošlo k poničení kloubů (kotníky aj.)
  • Pohyb končetin - cirkulace - prevence trombózy
  • Redukce otoků
  • Prevence proleženin polohováním
  • Stimulace regenerace dotekem a aktivací

Reorganization

Ischemic-infarction procedures in monkeys

  • Retained more finger flexion during food retrieval
  • After several months this deficit returned to preoperative levels
  • Movement representations underwent reorganization throughout the adjacent, undamaged cortex
  • Interaction between the damaged and undamaged areas
  • Changes in the motor areas of the cerebral cortex
    • Reorganization process of the brain [1]
  • Adult brains have the ability to change
    • Extent of the reorganization depends on the extent of the injury [1]


Physical therapy

  • At PT, you’ll learn exercises you can practice to stimulate spared neural pathways. A physical therapist helps guide you through exercises to target weakened muscles, and will teach you how to safely and effectively move around with your new deficitis.

Occupational therapy

  • OT helps individuals become more independent after injury by focusing on practicing activities of daily living. Activities of daily living are typically performed multiple times a day, making them a practical way to get your repetitions in.

Home exercises

  • Practicing physical therapy exercises at home and engaging in your activities of daily living as much as possible, is essential for optimizing neuroplasticity and functional improvements.

Botox injections

  • Many individuals with SCIs struggle with spasticity (involuntary muscle contractions), which affect their movements. Botox injections can help temporarily relieve these contractions, so individuals can focus on practicing their rehab exercises.

Orthotics

  • Orthotics like braces and splints can help promote correct musculoskeletal alignment and reduce the progression of spasticity.

Robot assisted therapy

  • Work by way of neuroplasticity [1]

Tirilazad mesylate

Multicenter trial of tirilazad mesylate in TBI

  • Experimental group was found to have similar mortality
    • Neurologic recovery rates when compared to placebo
  • Subgroup analysis suggested that tirilazad mesylate may contribute to reduced mortality in male patients with severe head injury accompanied by traumatic subarachnoid hemorrhage
    • (34% tirilazad group mortality versus 43% placebo group mortality)
  • www.intechopen.com/chapters/46049

Učení se prostorové orientaci

  • Changes in hippocampal structure
    • Associated with acquiring the knowledge of London's layout in local taxi drivers
  • A redistribution of grey matter was indicated in London Taxi Drivers compared to controls [1]

Virtual reality therapy


Vision improvements in adulhood

  • Prime examples of neuroplasticity
    • Recovering from amblyopia
    • Convergence insufficiency
    • Stereo vision anomalies
    • Binocular vision improvements
    • Stereopsis recovery [1]

VitamĂ­n C - ascorbic acid - AA

  • 30 to 70 mol/L serum in healthy humans in plasma
  • In the brain concentrations up to 3000 mol/L brain water
  • SVCT2 Na+-ascorbic acid transporter
    • Ubiquitously distributed on the cell membrane of the different tissues
    • Provides the electrogenic AA transport
      • Exploiting the favorable extracellular/intracellular sodium gradient

TBI animals

  • Level of AA in the cerebral tissue decreases rapidly following experimental TBI
    • Depletion is strictly dependent on the severity of the injury
    • Well below control values even longer after severe TBI
    • Returning to pre-impact concentrations after 72 h in mildly injured animals

Model of closed-head TBI, animals

  • Received pre-treatment with different doses of AA
    • Intraperitoneal 45 or 60 mg/kg/die for two weeks
    • Alone or in combination with equal dosages of tocopherol
  • For an additional 2 weeks after impact
  • AA, even if administered alone
    • Reduced mortality rate
    • Decreased cerebral tissue and circulating levels of malondialdehyde (MDA)
    • Restored brain values of AA
    • Stimulated tissue superoxide dismutase levels

Double blind controlled clinical trial, Razmkon et al.

  • Cohort of 100 TBI patients into 4 groups
    • Low dose of AA (500 mg/die i.v. for 7 days)
    • High dose of AA (10 g i.v. on admission and 4 days after, followed by 4 g/die i.v. for the remaining 3 days)
    • vitamin E (400 IU/die i.m. for 7 days)
    • Placebo
  • Beneficial effects of high dosage observed in AA-treated patients
    • Showed decreased progression of perilesional edema on CT scan.
  • The relatively modest effects of AA in this study might be:
    • Following TBI might perturb the functioning of the AA transporter,
      • Limiting the effectiveness of AA-based therapy
    • Decreased expression of SVCT2 occurs following TBI
    • Nebo snĂ­ĹženĂ­m vstupu vit. C do buněk při hyperglykemii ??

Vitamin C

Plasma vitamin C levels

  • Significantly lower in patients with brain trauma
    • Suggests that vitamin C plays a potential role in oxidative stress related to brain injury.
  • Other nutritional factors may play a role

Vitamin E (alpha-tocopherol)

A small study examining high-dose vitamin C and vitamin E

TBI, enteral nutrition enriched with antioxidants and neuromodulatory agents

Alpha-Tocopherol (Vitamin E)

  • Family of fat-soluble compounds
  • Tocopherols
    • Saturated hydrocarbon harbored side chain
  • Four tocotrienols
    • Unsaturated hydrocarbon harbored side chain
    • Composed by three isoprene units
  • Chromane ring, to which the hydrocarbon chain is bound
    • Oxido-reductive center common to all the eight compounds
  • Single OH-group
    • Can easily lose one electron, in the form of a hydrogen radical
      • Under the action of highly oxidizing ROS and RNS
        • Forming the corresponding, relatively stable, tocopheryl- or tocotrienyl-radical
  • The hydrophobic side chain of tocopherols
    • Allows these compounds to localize within the phospholipid bilayer of biological membranes
      • Interrupters of lipid peroxidation chain reactions
  • When oxidized by ROS and RNS, tocopheryl-radicals strictly depend on AA availability
    • To get recycled into their respective fully reduced forms
  • Among eight congeners, -tocopherol
    • Is the most abundant in the diet
  • Brain is rich in easily oxidizable fat-soluble compounds
    • Tissues with the lowest content of tocopherols
    • Potentially more exposed to lipid peroxidation

Clinical study tocopherol administration to TBI patients

Guinea pigs experiencing mild or severe TBI - Inci et al.

  • Tocopherol (100 mg/kg), intraperitoneally before graded TBI
    • Decreased brain levels of MDA
      • Derived from oxidative/nitrosative stress-mediated lipid peroxidation
  • Administered early post-injury is beneficial
    • To decrease tissue damage associated with TBI

Model of focal moderate TBI, Sprague–Dawley rats

  • Daily intraperitoneal injection of tocopherol (600 mg/kg) subsequently to TBI induction
  • Better on neurocognitive tests,
  • Had less evident histological signs of edema, inflammation, and necrosis
  • Decreased expression of Nogo-A and NgR
  • Tocopherol may reduce ROS-mediated tissue damage
    • May promote cerebral tissue regeneration following TBI

Model of focal moderate TBI in rats subjected to fluid percussion

  • Tocopheryl-succinate (100 mg/kg) + polyethylene glycol (PEG) (2 mL/kg)
  • Injected 30 min before or 5 min after injury
  • PEG alone improved the parameters under evaluation
  • Combination tocopheryl-succinate (100 mg/kg) + PEG (2mL/kg) showed the best
    • Increase in the survival rates
    • Best improvement of neurocognitive tasks and motor function
    • Decrease TBI-associated damage

Aiguo et al. rats

  • Regular diet with or without 500 IU/kg of -tocopherol for 4 weeks
  • At the end of which animals received focal mild TBI, according to the fluid percussion injury model
  • Tocopherol-rich diet prevented TBI-increased oxidative damage to proteins
    • SOD, Sir2, and BDNF caused by TBI
  • Improved TBI-associated motor function impairments
  • Dietary tocopherol supplementation could decrease the damaging effects of mild TBI on synaptic plasticity and cognitive functions.

Razmkon study - four groups of TBI patients

  • Tocopherol (400 IU/die intramuscularly for 7 days) showed a significant reduction of
    • Mortality rates
    • Improvement of long-term functional outcomes

Vitamin D (VDH; 1, 25-dihydroxyvitamin D3) + progesterone

  • Recognized as a neurosteroid
  • With downstream implications in many different CNS signaling cascades.

VDH deficiency - people

  • Is associated with dysregulated neuronal physiology
  • Exacerbate TBI
  • Reduce the efficacy of progesterone treatment for TBI
  • Relationship between VDH and TBI
  • Perhaps most important in aging populations
  • TBI in vitamin D generally acts in an anti-inflammatory manner
  • Regulating intracellular calcium levels
    • Reducing the effects of glutamate excitotoxicity
    • Enhancing free radical scavenging

Much TBI-related vitamin D research - combined therapy with progesterone in vitro

  • Two hormones are proposed to act in a synergistic
  • Perhaps compensatory manner
  • Each of them having their own anti-inflammatory and oxidative damage-reducing properties
  • VDH and progesterone
    • Stimulate neural growth in cultured neurons following in vitro glutamate excitotoxicity

Animal studies rat cortical contusion injury (CCI) models of TBI

  • Combined therapy consisting of VDH and progesterone
    • Resulted in reduced expression of inflammatory genes
    • Protection against cell death and DNA damage
    • Significant improvement in post-traumatic behavior in VDH-deficient rats

Clinical studies on VDH and progesterone combination therapy

  • Promising results
  • Improving outcomes and decreasing mortality rates after TBI
  • VDH has a high safety profile
  • Inexpensive and easily administered
  • Continued investigations will be critical to further elucidate its specific mechanisms
  • www.intechopen.com/chapters/46049

Zinc

Journal of Dietary Supplements

  • Supplementation improved clinical outcomes in patients with severe head trauma.
  • Study included 100 patients with severe head trauma
    • Ranging from 18 to 65 years of age
  • Participants received either a placebo or 120 mg of zinc
  • Had positive effects on
    • GOS SOFA score
    • Inflammatory markers in patients with severe head injury
  • Plasma zinc levels significantly increased in the zinc group as compared to the placebo
  • SOFA GOS and inflammation factors
    • Were significantly better in the zinc-supplemented group by day 16
  • Length of stay was shorter
  • Mortality was lower
  • blog.designsforhealth.com/node/91
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Poslední aktualizace: 4. 3. 2024 20:59:20