Hydrogen therapy: from mechanism to cerebral diseases

The medicinal value of hydrogen (H₂) was ignored prior to research illustrating that inhalation of 2% H₂ can significantly decrease the damage of cerebral ischemia/reperfusion caused by oxidative stress via selective elimination of hydroxyl freebase (OH) and peroxynitrite anion (ONOO-). Subsequently, there have been numerous experiments on H₂. Most research and trials involving the mechanisms underlying H₂ therapy show the effects of antioxygenation, anti-inflammation, and anti-apoptosis. Among quantities of diseases related with H₂ therapy, the brain disease is a hotspot as brain tissue and cell damage are easier to be induced by oxidative stress and other stimulations. In this review, emphasis is on stroke, traumatic brain injuries, and degenerative diseases, such as Alzheimer's disease and Parkinson's disease. Taking into account the blood-brain barrier, penetrability, possible side effects, and the molecular properties of H₂ within a single comprehensive review should contribute to advancing both clinical and non-clinical research and therapies. A systematic introduction of H₂ therapy with regards to mechanisms and cerebral diseases both in animal and human subjects can make it easier to comprehend H₂ therapy and therefore provide the basis for further clinical strategy.