Traumatic brain injuries (TBIs) are a leading cause of death and disability.
Sports-related TBIs are estimated to be more than several million per year. The
pathophysiology of TBIs involves high levels of inflammation, oxidative stress,
dysregulation of ion homeostasis, mitochondrial dysfunction, and apoptosis. There
is also a reduction in cerebral blood flow, leading to hypoxia and reduced
removal of metabolic waste, which further exacerbates the injury. There is
currently no recognized effective medical treatment or intervention for TBIs,
which may in part be due to the difficulty of drug delivery through the
blood-brain barrier. Molecular hydrogen has recently emerged as a neuroprotective
medical gas against cerebral infarction and neurodegenerative diseases including
TBIs. Its small molecular size and nonpolar nature allow it to easily diffuse
through the blood-brain barrier, cell membranes and subcellular compartments.
Hydrogen has been shown to exert selective anti-inflammatory, antioxidant, and
anti-apoptotic effects by regulating various transcription factors and protein
phosphorylation cascades. Nitric oxide is another well-recognized medical gas
that plays divergent roles in protecting from and in the recovery of TBIs, as
well as in contributing to their pathophysiology and injury. Excessive activation
of inducible nitric oxide synthase leads to excess inflammation and
oxidative/nitrosative damage as well as a paradoxical nitric oxide depletion in
the locations it is needed. Hydrogen regulates nitric oxide production and
metabolism, which enhances its benefits while reducing its harms. A novel
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