Neuroprotective Effects of Molecular Hydrogen: A Critical Review

Molecular hydrogen (H-2) is a physiologically inert gas. However, during the last 10 years, increasing evidence has revealed its biological functions under pathological conditions. More specifically, H(2)has protective effects against a variety of diseases, particularly nervous system disorders, which include ischemia/reperfusion injury, traumatic injury, subarachnoid hemorrhage, neuropathic pain, neurodegenerative diseases, cognitive dysfunction induced by surgery and anesthesia, anxiety, and depression. In addition, H(2)plays protective roles mainly through anti-oxidation, anti-inflammation, anti-apoptosis, the regulation of autophagy, and preservation of mitochondrial function and the blood-brain barrier. Further, H(2)is easy to use and has neuroprotective effects with no major side-effects, indicating that H(2)administration is a potential therapeutic strategy in clinical settings. Here we summarize the H(2)donors and their pharmacokinetics. Meanwhile, we review the effectiveness and safety of H(2)in the treatment of various nervous system diseases based on preclinical and clinical studies, leading to the conclusion that H(2)can be a simple and effective clinical therapy for CNS diseases such as ischemia-reperfusion brain injury, Parkinson's disease, and diseases characterized by cognitive dysfunction. The potential mechanisms involved in the neuroprotective effect of H(2)are also analyzed.