Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury

March 10, 2021

The results clearly demonstrate that HBOT can induce neuroplasticity and significant brain function improvement in mild TBI patients with prolonged Post-Concussion-Syndrome at late chronic stage, years after brain injury (1). 

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 involve diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging (1). Diffuse axonal injury- diffuse shearing of axonal pathways and small blood vessels - is one of the most common pathological feasures associated with mTBI (2). Another primary pathological feature, usually by a direct hit to the skull, is brain contusions, which commonly involve the frontal and anterior temporal lobes (3). Secondary pathologies of mTBI include ischemia, mild edema, and other bio-chemical and inflammatory processes culminating in impaired regenerative/healing processes resulted from increasing tissue hypoxia (4). Due to the diffuse nature of injury, cognitive impairments are usually the predominant symptoms, involving deficiencies in several cognitive functions, primarily memory, attention, processing speed, and exectuvie functions, all localized in multiple brain areas. Their potent functions rely on potent network structure and connectivity between different brain areas (5,6,7). 

The brain receives 15% of cardiac output, consumes 20% of the total body oxygen, and utlizes 25% of the total body glucose. Still, this energy supply is only sufficient to keep about five to ten percent of the neurons active at any given time. Thus, at standard healthy condition, at any given time the brain is utilizing almost all oxygen/energy delivered to it. The regeneration process after brain inury requires much addiitonal energy. This is where hyperbaric oxgyen treatment can help - the increased oxygen level in the blood and body tissues during treatment (8,9,10) can suupply the energy needed for brain repair. Indeed, several previous studies have demonstrated that elevated levels of dissolved oxygen by HBOT can have several reparative effects on damaged brain tissues (11,12,13,14,15,16,17,18). The elevated oxygen levels can have a significant effect on the brain metabolism, largely regulate by the glial cells. Improved energy management leads to multifaceted repair, including activation of angiogenesis and triggering of neuroplasticity (reactivation of quiescent neurons; creation of new synapses and new axonal connections), and might even induce differentation of neuronal stem cells (15). The idea that HBOT can promote brain repair is reasonable and has gained experimental support (1)

The HBOT option has been dismissed by the medical community on grounds of 1. Lack of knowledge about the connection between metabolism and neuroplasticity. 2. Lack of randomized clinical trial with standard placebo control. 3. Sham control with room air at 2.3 Atm yeilded significant improvements. (1)

A recent study of HBOT for mTBI compared the effect of 100% oxgyen at 2.4 Atm with the effect of room air at 1.3Atm as sham control (36). The study found signifcant improvements in both groups and with slightly higher efficacy at 1.3 Atm (1).

Room air at 1.3Atm cannot serve as a proper sham-control since it is not "ineffectual treatment) (as is required of placebo) since it leads to a significant increase in the level of tissue oxygenation which has been shown to be effective (19,20). 100% oxgyen at 2.4 Atm leads to too high oxygen levels which can cause inhibitory or even focal toxicity. 

(1) Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury - Randomized Prospective Trial. Rahav Boussi-Gross. November 2013, Volume 9, Issue 11

(2) Medana IM, Esiri MM (2003) Axonal damage: a key predictor of outcome in human CNS diseases. Brain: a journal of neurology 126: 515–530. [PubMed] [Google Scholar]

(3) Kushner D (1998) Mild traumatic brain injury: toward understanding manifestations and treatment. Archives of internal medicine 158: 1617–1624. [PubMed] [Google Scholar]

(4) Kochanek PM, Clark R.S.B., & Jenkins L.W. (2007) TBI:Pathobiology. In: Zasler ND, Katz, D.I, Zafonte, R.D., editor. Brain injury medicine. NY: Demos medical publishing. pp. 81–92.

(5) Kushner D (1998) Mild traumatic brain injury: toward understanding manifestations and treatment. Archives of internal medicine 158: 1617–1624. [PubMed] [Google Scholar]

(6) Levin HS, Mattis S, Ruff RM, Eisenberg HM, Marshall LF, et al. (1987) Neurobehavioral outcome following minor head injury: a three-center study. Journal of neurosurgery 66: 234–243. [PubMed][Google Scholar]

(7) Sohlberg MM, Mateer CA (2001) Cognitive Rehabilitation: An Integrative Neuropsychological Approach. NY: The Guilford Press.

(8) Niklas A, Brock D, Schober R, Schulz A, Schneider D (2004) Continuous measurements of cerebral tissue oxygen pressure during hyperbaric oxygenation—HBO effects on brain edema and necrosis after severe brain trauma in rabbits. J Neurol Sci 219: 77–82. [PubMed] [Google Scholar]

(9) Reinert M, Barth A, Rothen HU, Schaller B, Takala J, et al.. (2003) Effects of cerebral perfusion pressure and increased fraction of inspired oxygen on brain tissue oxygen, lactate and glucose in patients with severe head injury. Acta Neurochir (Wien) 145: : 341–349; discussion 349–35. [PubMed][Google Scholar]

(10) Calvert JW, Cahill J, Zhang JH (2007) Hyperbaric oxygen and cerebral physiology. Neurol Res 29:132–141. [PubMed] [Google Scholar]

(11) Efrati S, Fishlev G, Bechor Y, Volkov O, Bergan J, et al. (2013) Hyperbaric oxygen induces late neuroplasticity in post stroke patients - randomized, prospective trial. PloS one 8: e53716.[PMC free article] [PubMed] [Google Scholar]

(12) Calvert JW, Cahill J, Zhang JH (2007) Hyperbaric oxygen and cerebral physiology. Neurol Res 29:132–141. [PubMed] [Google Scholar]

(13) Neubauer RA, James P (1998) Cerebral oxygenation and the recoverable brain. Neurol Res 20 Suppl 1S33–36. [PubMed] [Google Scholar]

(14) Golden ZL, Neubauer R, Golden CJ, Greene L, Marsh J, et al. (2002) Improvement in cerebral metabolism in chronic brain injury after hyperbaric oxygen therapy. Int J Neurosci 112: 119–131.[PubMed] [Google Scholar]

(15) Zhang JH, Lo T, Mychaskiw G, Colohan A (2005) Mechanisms of hyperbaric oxygen and neuroprotection in stroke. Pathophysiology 12: 63–77. [PubMed] [Google Scholar]

(16) Gunther A, Kuppers-Tiedt L, Schneider PM, Kunert I, Berrouschot J, et al. (2005) Reduced infarct volume and differential effects on glial cell activation after hyperbaric oxygen treatment in rat permanent focal cerebral ischaemia. Eur J Neurosci 21: 3189–3194. [PubMed] [Google Scholar]

(17) Yang YJ, Wang XL, Yu XH, Wang X, Xie M, et al. (2008) Hyperbaric oxygen induces endogenous neural stem cells to proliferate and differentiate in hypoxic-ischemic brain damage in neonatal rats. Undersea Hyperb Med 35: 113–129. [PubMed] [Google Scholar]

(18) Rockswold SB, Rockswold GL, Zaun DA, Zhang X, Cerra CE, et al. (2010) A prospective, randomized clinical trial to compare the effect of hyperbaric to normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen toxicity in severe traumatic brain injury. Journal of neurosurgery 112: 1080–1094. [PubMed] [Google Scholar]

(19) Collet JP, Vanasse M, Marois P, Amar M, Goldberg J, et al. (2001) Hyperbaric oxygen for children with cerebral palsy: a randomised multicentre trial. HBO-CP Research Group. Lancet 357: 582–586.[PubMed] [Google Scholar]

(20) James PB (2001) Hyperbaric oxygenation for cerebral palsy. Lancet 357: 2052–2053. [PubMed][Google Scholar]