The high morbidity, high mortality, and significant shortage of effective
therapies for
subarachnoid hemorrhage (SAH) have created an urgency to discover novel
therapies. Human studies in Asia have established the safety of
hydrogen gas in the treatment of hepatic, renal, pulmonary, and
cardiac diseases. Mechanistically,
hydrogen gas has been shown to affect oxidative stress,
inflammation, and apoptosis. We hypothesized that
hydrogen therapy would improve neurological function and increase survival rate in SAH. High dose
hydrogen gas (66% at 3 L/min) was administered for 2 hours at 0.5, 8, and 18 hours after SAH. This treatment increased 72-hour survival rate and provided 24-hour neuroprotection after SAH in rats. To our knowledge, this is the first report demonstrating that high dose
hydrogen gas
therapy reduces mortality and improves outcome after SAH. Our results correlate well with the proposed mechanisms of
hydrogen gas
therapy within the literature. We outline four pathways and downstream targets of
hydrogen gas potentially responsible for our results. A potentially complex network of pathways responsible for the efficacy of
hydrogen gas
therapy, along with a limited mechanistic understanding of these pathways, justifies further investigation to provide a basis for clinical trials and the advancement of
hydrogen gas
therapy in humans. This study was approved by the Institutional Animal Care and Use Committee of Loma Linda University, USA (Approval No. 8160016) in May 2016.