Hyperbaric oxygen therapy and cerebral ischemia: Neuroprotective mechanisms

Introduction: Numerous studies have demonstrated a protective effect of hyperbaric oxygen therapy in experimental ischemic brain injury, and many physiological and molecular mechanisms of hyperbaric oxygen therapy-related neuroprotection have been identified. Methods: Review of articles pertaining to hyperbaric oxygen therapy and cerebral ischemia in the National Library of Medicine and National Institutes of Health database, emphasizing mechanisms of hyperbaric oxygen therapy-related neuroprotection. Results: Hyperbaric oxygen therapy has been shown to ameliorate brain injury in a variety of animal models including focal cerebral ischemia, global cerebral ischemia, neonatal hypoxia- ischemia and subarachnoid hemorrhage. Small human trials of hyperbaric oxygen therapy in focal ischemia have not shown benefit, although one trial of hyperbaric oxygen therapy before cardiopulmonary bypass demonstrated improved neuropsychological and inflammatory outcomes with hyperbaric oxygen therapy. Hyperbaric oxygen therapy is associated with improved cerebral oxygenation, reduced blood-brain barrier breakdown, decreased inflammation, reduced cerebral edema, decreased intracranial pressure, reduced oxidative burden, reduced metabolic derangement, decreased apoptotic cell death and increased neural regeneration. Conclusion: On a molecular level, hyperbaric oxygen therapy leads to activation of ion channels, inhibition of hypoxia inducible factor-la, up-regulation of Bcl-2, inhibition of MMP-9, decreased cyclooxygenase-2 activity, decreased myeloperoxidase activity, up-regulation of superoxide dismutase and inhibition of Nogo-A (an endogenous growth-inhibitory factor). Ongoing research will continue to describe the mechanisms of hyperbaric oxygen therapy- related neuroprotection, and possibly expand hyperbaric oxygen therapy use clinically.