Neuroprotective Effects of Molecular Hydrogen: A Critical Review

Abstract

Molecular hydrogen (H2) is a physiologically inert gas. However, during the last 10 years, increasing evidence has revealed its biological functions under pathological conditions. More specifically, H2 has protec- tive effects against a variety of diseases, particularly nervous system disorders, which include ischemia/reperfu- sion injury, traumatic injury, subarachnoid hemorrhage, neuropathic pain, neurodegenerative diseases, cognitive dysfunction induced by surgery and anesthesia, anxiety, and depression. In addition, H2 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, H2 is easy to use and has neuroprotective effects with no major side-effects, indicating that H2 administra- tion is a potential therapeutic strategy in clinical settings. Here we summarize the H2 donors and their pharmacoki- netics. Meanwhile, we review the effectiveness and safety of H2 in the treatment of various nervous system diseases based on preclinical and clinical studies, leading to the conclusion that H2 can be a simple and effective clinical therapy for CNS diseases such as ischemia-reperfusion brain injury, Parkinson’s disease, and diseases character- ized by cognitive dysfunction. The potential mechanisms involved in the neuroprotective effect of H2 are also analyzed.

Study details

Article type

Review

Disease / injury model

Neurological diseases (ischemia/reperfusion injury, traumatic injury, subarachnoid hemorrhage, neuropathic pain, Parkinson's disease, Alzheimer's disease, cognitive dysfunction, mood disorders)

Dose comparison

The review notes that only a few studies have focused on dose- and time-dependent effects and tolerance to H2 in basic and clinical studies. It also mentions that higher H2 concentrations in target tissues may yield better therapeutic effects, as seen with Pd hydride nanoparticles versus traditional administration routes in Alzheimer's models.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Molecular hydrogen (H2) demonstrates neuroprotective effects in a wide range of neurological diseases, including ischemia/reperfusion injury, traumatic injury, subarachnoid hemorrhage, neuropathic pain, neurodegenerative diseases (such as Parkinson's and Alzheimer's), cognitive dysfunction, anxiety, and depression. The mechanisms involve anti-oxidation, anti-inflammation, anti-apoptosis, regulation of autophagy, and preservation of mitochondrial function and the blood-brain barrier. H2 is generally safe, with few reported side effects, and shows promise as a therapeutic strategy for CNS diseases in both preclinical and clinical studies.