Concussion & Mild TBI

Recent years have brought an increased focus to concussions and other traumatic brain injuries in the United States.1 Signs of a concussion include slow response times, irritability, low energy. These symptoms may resolve on their own but can persist and evolve into long-lasting cognitive, behavioral, and communicative disabilities.However, advances in medical research suggest hyperbaric oxygen therapy (HBOT) has the potential to slow or reverse concussion symptoms.

Hyperbaric oxygen therapy works to reduce or eliminate concussion symptoms by infusing blood with higher than average levels of oxygen.3 Extra oxygen boosts mitochondria activity and energizes growth of new blood vessels in the brain.4 Scientists have linked increased mitochondrial activity to healing in various tissues throughout the body.4

HBOT Research Shows Improvement to:

  • Headaches caused by damaged nerve fibers
  • Memory loss (most improvement)
  • Difficulty problem-solving
  • Anxiety/depression
  • Shortened attention span (significant improvement)
  • Slowed reaction time

Concussion & Mild TBI

Recent years have brought an increased focus to concussions and other traumatic brain injuries in the United States.1 Signs of a concussion include slow response times, irritability, low energy. These symptoms may resolve on their own but can persist and evolve into long-lasting cognitive, behavioral, and communicative disabilities.However, advances in medical research suggest hyperbaric oxygen therapy (HBOT) has the potential to slow or reverse concussion symptoms.

Hyperbaric oxygen therapy works to reduce or eliminate concussion symptoms by infusing blood with higher than average levels of oxygen.3 Extra oxygen boosts mitochondria activity and energizes growth of new blood vessels in the brain.4 Scientists have linked increased mitochondrial activity to healing in various tissues throughout the body.4

HBOT Research Shows Improvement to:

  • Headaches caused by damaged nerve fibers
  • Memory loss (most improvement)
  • Difficulty problem-solving
  • Anxiety/depression
  • Shortened attention span (significant improvement)
  • Slowed reaction time

Benefits of HBOT for Concussion / Mild TBI:

Increases Amount of Oxygen in the Blood

Stimulates development of new blood vessels from pre-existing vessels as well as the natural development of new blood vessels.

Reduces Inflammation & Swelling

Suppresses the cellular activity of the immune system which triggers swelling when an injury or damage to the body occurs.  While this reaction is meant to start healing and protect from injury it can result in secondary injury, pain, and prolonged recovery time.

Preserves, Repairs, & Enhances Cellular Functions

Boosts cellular metabolism, promotes rapid cell reproduction, and enhances collagen synthesis. Collagen is a protein in connective tissues like skin.

Accelerates Wound Healing

Increases production of nitric oxide in the bone marrow and microvasculature (smaller blood vessels). Stimulates stem cells from the bone marrow, accelerating wound healing. Dilation of smaller blood vessels enhances blood flow to areas of local tissue damage, hypoxia, and ischemia.

Key Research on Hyperbaric Oxygen Treatment for Concussion

The National Brain Injury Rescue and Rehabilitation Study – a multicenter observational study of hyperbaric oxygen for mild traumatic brain injury with post-concussive symptoms

The National Brain Injury Rescue and Rehabilitation Project was established as a preliminary study to test the safety and practicality of multi-center hyperbaric oxygen administration for the post-concussive symptoms of chronic mild traumatic brain injury as a precursor to a pivotal, independent, multi-center, controlled clinical trial. This report presents the results for 32 subjects who completed a preliminary trial of hyperbaric oxygen several years before the passage of the 21 st Century Cures Act. This study anticipated the Act and its reassessment of clinical research. Subjects received 40-82 one-hour treatments at 1.5 atmospheres absolute 100% oxygen. Outcome measures included repeated self-assessment measures and automated neurocognitive tests. The subjects demonstrated improvement in 21 of 25 neurocognitive test measures observed. The objective neurocognitive test components showed improvement in 13 of 17 measures. Earlier administration of hyperbaric oxygen post injury, younger age at the time of injury and hyperbaric oxygen administration, military status, and increased number of hyperbaric oxygen administrations were characteristics associated with improved outcomes. There were no adverse events. Hyperbaric oxygen was found to be safe, inexpensive and worthy of clinical application in the 21 st Century model of facile data collection provided by recent research regulatory shifts in medicine. The study was approved by the ethics review committee of the Western Institutional Review Board (WIRB; Protocol #20090761).

Case control study: hyperbaric oxygen treatment of mild traumatic brain injury persistent post-concussion syndrome and post-traumatic stress disorder.

Mild traumatic brain injury (TBI) persistent post-concussion syndrome (PPCS) and post-traumatic stress disorder (PTSD) are epidemic in United States Iraq and Afghanistan War veterans. Treatment of the combined diagnoses is limited. The aim of this study is to assess safety, feasibility, and effectiveness of hyperbaric oxygen treatments (HBOT) for mild TBI PPCS and PTSD. Thirty military subjects aged 18-65 with PPCS with or without PTSD and from one or more blast-induced mild-moderate traumatic brain injuries that were a minimum of 1 year old and occurred after 9/11/2001 were studied. The measures included symptom lists, physical exam, neuropsychological and psychological testing on 29 subjects (1 dropout) and SPECT brain imaging pre and post HBOT.

Increased circulating stem cells and better cognitive performance in traumatic brain injury subjects following hyperbaric oxygen therapy.

Traumatic brain injury (TBI) may cause persistent cognitive dysfunction. A pilot clinical study was performed to determine if hyperbaric oxygen (HBO₂) treatment improves cognitive performance. It was hypothesized that stem cells, mobilized by HBO₂ treatment, are recruited to repair damaged neuronal tissue. This hypothesis was tested by measuring the relative abundance of stem cells in peripheral blood and cognitive performance during this clinical trial. The subject population consisted of 28 subjects with persistent cognitive impairment caused by mild to moderate TBI suffered during military deployment to Iraq or Afghanistan. Fluorescence-activated cell sorting (FACS) analysis was performed for stem cell markers in peripheral blood and correlated with variables resulting from standard tests of cognitive performance and post-traumatic stress disorder: ImPACT, BrainCheckers and PCL-M test results. HBO₂ treatment correlated with stem cell mobilization as well as increased cognitive performance. Together these results support the hypothesis that stem cell mobilization may be required for cognitive improvement in this population.

Hyperbaric Oxygen Therapy Can Induce Angiogenesis and Regeneration of Nerve Fibers in Traumatic Brain Injury Patients.

Background: Recent clinical studies in stroke and traumatic brain injury (TBI) victims suffering chronic neurological injury present evidence that hyperbaric oxygen therapy (HBOT) can induce neuroplasticity. Objective: To assess the neurotherapeutic effect of HBOT on prolonged post-concussion syndrome (PPCS) due to TBI, using brain microstructure imaging. Methods: Fifteen patients afflicted with PPCS were treated with 60 daily HBOT sessions. Imaging evaluation was performed using Dynamic Susceptibility Contrast-Enhanced (DSC) and Diffusion Tensor Imaging (DTI) MR sequences. Cognitive evaluation was performed by an objective computerized battery (NeuroTrax). Results: HBOT was initiated 6 months to 27 years (10.3 ± 3.2 years) from injury. After HBOT, DTI analysis showed significantly increased fractional anisotropy values and decreased mean diffusivity in both white and gray matter structures. In addition, the cerebral blood flow and volume were increased significantly. Clinically, HBOT induced significant improvement in the memory, executive functions, information processing speed and global cognitive scores. Conclusions: The mechanisms by which HBOT induces brain neuroplasticity can be demonstrated by highly sensitive MRI techniques of DSC and DTI. HBOT can induce cerebral angiogenesis and improve both white and gray microstructures indicating regeneration of nerve fibers. The micro structural changes correlate with the neurocognitive improvements.

Hyperbaric oxygen therapy for traumatic brain injury: bench-to-bedside.

Traumatic brain injury (TBI) is a serious public health problem in the United States. Survivors of TBI are often left with significant cognitive, behavioral, and communicative disabilities. So far there is no effective treatment/intervention in the daily clinical practice for TBI patients. The protective effects of hyperbaric oxygen therapy (HBOT) have been proved in stroke; however, its efficiency in TBI remains controversial. In this review, we will summarize the results of HBOT in experimental and clinical TBI, elaborate the mechanisms, and bring out our current understanding and opinions for future studies.

Treatment of persistent post-concussion syndrome due to mild traumatic brain injury: current status and future directions.

Persistent post-concussion syndrome caused by mild traumatic brain injury has become a major cause of morbidity and poor quality of life. Unlike the acute care of concussion, there is no consensus for treatment of chronic symptoms. Moreover, most of the pharmacologic and non-pharmacologic treatments have failed to demonstrate significant efficacy on both the clinical symptoms as well as the pathophysiologic cascade responsible for the permanent brain injury. This article reviews the pathophysiology of PCS, the diagnostic tools and criteria, the current available treatments including pharmacotherapy and different cognitive rehabilitation programs, and promising new treatment directions. A most promising new direction is the use of hyperbaric oxygen therapy, which targets the basic pathological processes responsible for post-concussion symptoms; it is discussed here in depth.

Clinical results in brain injury trials using HBO2 therapy: Another perspective.

The current debate surrounding the use of hyperbaric oxygen (HBO2) for neurological indications, specifically mild to moderate chronic traumatic brain injury (mTBI) and post-concussion syndrome (PCS), is mired in confusion due to the use of non-validated controls and an unfamiliarity by many practitioners of HBO2 therapy with the experimental literature. In the past 40 years, the use of an air sham (21% oxygen, 1.14-1.5 atmospheres absolute/atm abs) in clinical and animal studies, instead of observational or crossover controls, has led to false acceptance of the null hypothesis (declaring no effect when one is present), due to the biological activity of these “sham” controls. The recent Department of Defense/Veterans Administration (DoD/VA) sponsored trials, previous published reports on the use of HBO2 therapy on stroke and mTBI and preliminary reports from the HOPPS Army trial, have helped to highlight the biological activity of pressurized air, validate the development of a convincing control for future studies and demonstrate the effectiveness of a hyperbaric intervention for mTBI/ PCS. Approval of HBO2 for neurological indications, especially for mTBI/PCS, should be granted at the federal, state and certifying body levels as a safe and viable treatment for recovery in the post-acute phase.

Hyperbaric oxygen therapy for the treatment of traumatic brain injury: a meta-analysis.

Compelling evidence suggests the advantage of hyperbaric oxygen therapy (HBOT) in traumatic brain injury. The present meta-analysis evaluated the outcomes of HBOT in patients with traumatic brain injury (TBI). Prospective studies comparing hyperbaric oxygen therapy vs. control in patients with mild (GCS 13-15) to severe (GCS 3-8) TBI were hand-searched from medical databases using the terms “hyperbaric oxygen therapy, traumatic brain injury, and post-concussion syndrome”. Glasgow coma scale (GCS) was the primary outcome, while Glasgow outcome score (GOS), overall mortality, and changes in post-traumatic stress disorder (PTSD) score, constituted the secondary outcomes. The results of eight studies (average age of patients, 23-41 years) reveal a higher post-treatment GCS score in the HBOT group (pooled difference in means = 3.13, 95 % CI 2.34-3.92, P < 0.001), in addition to greater improvement in GOS and lower mortality, as compared to the control group. However, no significant change in the PTSD score was observed. Patients undergoing hyperbaric therapy achieved significant improvement in the GCS and GOS with a lower overall mortality, suggesting its utility as a standard intensive care regimen in traumatic brain injury.

Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury – randomized prospective trial.

Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments. The trial population included 56 mTBI patients 1-5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups.

Hyperbaric oxygen therapy (1.5 ATA) in treating sports related TBI/CTE: two case reports.

Despite adequate evidence, including randomized controlled trials; hyperbaric oxygen is not yet recognized as efficacious for treating various forms of brain injury, specifically traumatic brain injury. Political-economic issues have kept this benign therapy from being widely adopted despite the lack of viable alternatives. Two football players with TBI/CTE are herewith shown to benefit from being treated with hyperbaric oxygen as documented by neurocognitive examinations and functional brain imaging, in one case treatment commenced decades after the brain injury. Perhaps the interest in HBOT by those participating in high-risk sports will help expand this orphan therapy into mainstream medicine.

Recent News on Hyberbaric Oxygen Treatment for Concussion

Additional Research

The National Brain Injury Rescue and Rehabilitation Study – a multicenter observational study of hyperbaric oxygen for mild traumatic brain injury with post-concussive symptoms

The National Brain Injury Rescue and Rehabilitation Project was established as a preliminary study to test the safety and practicality of multi-center hyperbaric oxygen administration for the post-concussive symptoms of chronic mild traumatic brain injury as a precursor to a pivotal, independent, multi-center, controlled clinical trial. This report presents the results for 32 subjects who completed a preliminary trial of hyperbaric oxygen several years before the passage of the 21 st Century Cures Act. This study anticipated the Act and its reassessment of clinical research. Subjects received 40-82 one-hour treatments at 1.5 atmospheres absolute 100% oxygen. Outcome measures included repeated self-assessment measures and automated neurocognitive tests. The subjects demonstrated improvement in 21 of 25 neurocognitive test measures observed. The objective neurocognitive test components showed improvement in 13 of 17 measures. Earlier administration of hyperbaric oxygen post injury, younger age at the time of injury and hyperbaric oxygen administration, military status, and increased number of hyperbaric oxygen administrations were characteristics associated with improved outcomes. There were no adverse events. Hyperbaric oxygen was found to be safe, inexpensive and worthy of clinical application in the 21 st Century model of facile data collection provided by recent research regulatory shifts in medicine. The study was approved by the ethics review committee of the Western Institutional Review Board (WIRB; Protocol #20090761).

read more

Erratum: Effect of hyperbaric oxygenation therapy on post-concussion syndrome.

The present review evaluated the effect of hyperbaric oxygenation (HBO) therapy on post-concussion syndrome (PCS). Searches for publications from the earliest date possible up until the first week of 2016 were conducted using the electronic databases Cochrane, EBSCOhost, Embase, Ovid MEDLINE, PubMed and Web of Science. Additional trials were identified through reference list scanning. Randomized controlled trials assessing the effectiveness of HBO therapy in PCS were selected and tested for eligibility for inclusion in the present review.

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Effect of hyperbaric oxygen therapy on chronic neurocognitive deficits of post-traumatic brain injury patients: retrospective analysis.

The aim of the study is to evaluate the effect of hyperbaric oxygen therapy (HBOT) in participants suffering from chronic neurological deficits due to traumatic brain injury (TBI) of all severities in the largest cohort evaluated so far with objective cognitive function tests and metabolic brain imaging. A retrospective analysis was conducted of 154 patients suffering from chronic neurocognitive damage due to TBI, who had undergone computerised cognitive evaluations pre-HBOT and post-HBOT treatment. The average age was 42.7-14.6 years, and 58.4% were men. All patients had documented TBI 0.3-33 years (mean 4.6-5.8, median 2.75 years) prior to HBOT. HBOT was associated with significant improvement in all of the cognitive domains, with a mean change in global cognitive scores of 4.6-8.5 (p<0.00001).

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Evidence brief: hyperbaric oxygen therapy (HBOT) for traumatic brain injury and/or post-traumatic stress disorder.

This report is a product of the VA Evidence-based Synthesis Program. The purpose is to provide “timely and accurate syntheses of targeted healthcare topics. to improve the health and healthcare of Veterans”. The authors have made a comprehensive search and analysis of the literature and make recommendations to assist clinicians in dealing with veterans suffering from either traumatic brain injury (TBI) or post-traumatic stress disorder (PTSD). The report is timely and of great potential impact given the vigorous and lengthy debate among hyperbaric physicians and lay people determined to find an answer for the large numbers of veterans deeply affected with some combination of PTSD and post-concussion dysfunction.

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HYPERBARIC OXYGEN THERAPY- BASICS AND NEW APPLICATIONS

Hyperbaric oxygen therapy (HBOT) serves as primary or adjunctive therapy for a diverse range of medical conditions. The indication for HBOT can be related to either pressure (decompression sickness or air emboli) or tissue hypoxia. It is now realized, that the combined action of hyperoxia and hyperbaric pressure, leads to significant improvement in tissue oxygenation while targeting both oxygen and pressure sensitive genes, resulting in improved mitochondrial metabolism with anti-apoptotic and anti-inflammatory effects. Clinical studies published in recent year’s present convincing evidence that HBOT can be the coveted neurotherapeutic method for brain repair. Here we discuss the multi-faceted role of HBOT in wound care in general and in neurotherapeutics in detail.

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The protection effect and mechanism of hyperbaric oxygen therapy in rat brain with traumatic injury.

To investigate the effect of hyperbaric oxygen therapy (HBOT) on traumatic brain injury (TBI) outcome. The modified Marmarou’s weight drop device was used to generate non-lethal moderate TBI rat model, and further developed in vitro astrocytes culturing system. Then, we analyzed the expression changes of interested genes and protein by quantitative PCR and western blot. Multiple HBO treatments significantly reduced the expression of apoptosis promoting genes, such as c-fos, c-jun, Bax and weakened the activation of Caspase-3 in model rats. On the contrary, HBOT alleviated the decrease of anti-apoptosis gene Bcl-2 and promoted the expression of neurotrophic factors (NTFs), such as NGF, BDNF, GDNF and NT-3 in vivo. As a consequent, the neuropathogenesis was remarkably relied with HBOT.

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Case control study: hyperbaric oxygen treatment of mild traumatic brain injury persistent post-concussion syndrome and post-traumatic stress disorder.

Mild traumatic brain injury (TBI) persistent post-concussion syndrome (PPCS) and post-traumatic stress disorder (PTSD) are epidemic in United States Iraq and Afghanistan War veterans. Treatment of the combined diagnoses is limited. The aim of this study is to assess safety, feasibility, and effectiveness of hyperbaric oxygen treatments (HBOT) for mild TBI PPCS and PTSD. Thirty military subjects aged 18-65 with PPCS with or without PTSD and from one or more blast-induced mild-moderate traumatic brain injuries that were a minimum of 1 year old and occurred after 9/11/2001 were studied. The measures included symptom lists, physical exam, neuropsychological and psychological testing on 29 subjects (1 dropout) and SPECT brain imaging pre and post HBOT.

read more

Increased circulating stem cells and better cognitive performance in traumatic brain injury subjects following hyperbaric oxygen therapy.

Traumatic brain injury (TBI) may cause persistent cognitive dysfunction. A pilot clinical study was performed to determine if hyperbaric oxygen (HBO₂) treatment improves cognitive performance. It was hypothesized that stem cells, mobilized by HBO₂ treatment, are recruited to repair damaged neuronal tissue. This hypothesis was tested by measuring the relative abundance of stem cells in peripheral blood and cognitive performance during this clinical trial. The subject population consisted of 28 subjects with persistent cognitive impairment caused by mild to moderate TBI suffered during military deployment to Iraq or Afghanistan. Fluorescence-activated cell sorting (FACS) analysis was performed for stem cell markers in peripheral blood and correlated with variables resulting from standard tests of cognitive performance and post-traumatic stress disorder: ImPACT, BrainCheckers and PCL-M test results. HBO₂ treatment correlated with stem cell mobilization as well as increased cognitive performance. Together these results support the hypothesis that stem cell mobilization may be required for cognitive improvement in this population.

read more

Hyperbaric oxygen for mild traumatic brain injury: Design and baseline summary.

The Brain Injury and Mechanisms of Action of Hyperbaric Oxygen for Persistent Post-Concussive Symptoms after Mild Traumatic Brain Injury (mTBI) (BIMA) study, sponsored by the Department of Defense, is a randomized double-blind, sham-controlled clinical trial that has a longer duration of follow-up and more comprehensive assessment battery compared to recent HBO₂ studies. BIMA randomized 71 participants from September 2012 to May 2014. Primary results are expected in 2017. Randomized military personnel received hyperbaric oxygen (HBO₂) at 1.5 atmospheres absolute (ATA) or sham chamber sessions at 1.2 ATA, air, for 60 minutes daily for 40 sessions. Outcomes include neuropsychological, neuroimaging, neurological, vestibular, autonomic function, electroencephalography, and visual systems evaluated at baseline, immediately following intervention at 13 weeks and six months with self-report symptom and quality of life questionnaires at 12 months, 24 months and 36 months. Characteristics include: median age 33 years (range 21-53); 99% male; 82% Caucasian; 49% diagnosed post-traumatic stress disorder; 28% with most recent injury three months to one year prior to enrollment; 32% blast injuries; and 73% multiple injuries. This manuscript describes the study design, outcome assessment battery, and baseline characteristics. Independent of a therapeutic role of HBO₂, results of BIMA will aid understanding of mTBI.

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Review of recent non-hyperbaric oxygen interventions for mild traumatic brain injury.

Traumatic brain injury (TBI) affects 3.2 to 5.3 million persons in the United States (U.S.), and the impact in the U.S. military is proportionally higher. Consensus is lacking regarding an accepted outcome to measure the effectiveness of interventions to improve the symptoms associated with TBI, and no standard-of-care treatment exists for mild TBI (mTBI). A recent literature review evaluated hyperbaric oxygen therapy (HBO₂) interventions, and findings were mixed. We conducted a systematic review of non-HBO₂ mTBI interventional trials published in 2005-2015 in military and civilian populations. A total of 154 abstracts, seven randomized controlled trials (RCTs) and five pilot studies were reviewed. RCTs were evaluated using Consolidated Standards of Reporting Trials criteria. Results indicated that studies published within the period of review were small pilot studies for rehabilitation therapy and motion capture or virtual reality gaming interventions. Neuropsychological assessments were commonly specified outcomes, and most studies included a combination of symptom and neuropsychological assessments. Findings indicated a lack of large-scale, well-controlled trials to address the symptoms and sequelae of this condition, but results of small exploratory studies show evidence of potentially promising interventions.

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References
  1. Our Mission. (n.d.). Retrieved March 27, 2018, from https://concussion.weillcornell.org/about-us/our-mission
  2. Hu, Q., Manaenko, A., Xu, T., Guo, Z., Tang, J., & Zhang, J. H. (2016). Hyperbaric oxygen therapy for traumatic brain injury: bench-to-bedside. Medical Gas Research, 6(2), 102.
  3. Tal, S., Hadanny, A., Sasson, E., Suzin, G., & Efrati, S. (2017). Hyperbaric oxygen therapy can induce angiogenesis and regeneration of nerve fibers in traumatic brain injury patients. Frontiers in Human Neuroscience, 11, 508.
  4. Keilman, J. (2012, November 14). Concussions: What happens and how the brain heals. Retrieved March 29, 2018, from http://articles.chicagotribune.com/2012-11-14/news/ct-met-concussions-1114-20121114_1_concussion-program-david-hovda-cells
  5. Stoller, K. P. (2011). Hyperbaric oxygen therapy (1.5 ATA) in treating sports related TBI/CTE: two case reports. Medical Gas Research, 1(1), 17.
  6. Boussi-Gross R, Golan H, Fishlev G, Bechor Y, Volkov O, Bergan J, Friedman M, Hoofien D, Shlamkovitch N, Ben-Jacob E, Efrati S (2013) Hyperbaric oxygen therapy can improve post-concussion syndrome years after mild traumatic brain injury- randomized prospective trial. PLoS One 8(11):e79995
  7. Shandley, S., Wolf, E. G., Schubert-Kappan, C. M., Baugh, L. M., Richards, M. F., Prye, J., & Kalns, J. (2017). Increased circulating stem cells and better cognitive performance in traumatic brain injury subjects following hyperbaric oxygen therapy. Undersea & Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Medical Society, Inc, 44(3), 257-269.
  8. Wang, F., Wang, Y., Sun, T., & Yu, H. L. (2016). Hyperbaric oxygen therapy for the treatment of traumatic brain injury: a meta-analysis. Neurological Sciences, 37(5), 693-701.
  9. Tal, S., Hadanny, A., Sasson, E., Suzin, G., & Efrati, S. (2017). Hyperbaric oxygen therapy can induce angiogenesis and regeneration of nerve fibers in traumatic brain injury patients. Frontiers in Human Neuroscience, 11, 508.

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