Neuroprotective Effects of Molecular Hydrogen: A Critical Review
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REVIEW
Neuroprotective Effects of Molecular Hydrogen: A Critical Review Wei Chen1,2 • Han-Ting Zhang3 • Shu-Cun Qin1,2
Received: 19 February 2020 / Accepted: 31 May 2020 Ó Shanghai Institutes for Biological Sciences, CAS 2020
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 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, H2 plays protective roles mainly through anti-oxidation, anti-inflammation, antiapoptosis, 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 administration is a potential therapeutic strategy in clinical settings. Here we summarize the H2 donors and their pharmacokinetics. Meanwhile, we review the effectiveness and safety of H2 in the treatment of various nervous system diseases & Han-Ting Zhang [email protected] & Shu-Cun Qin [email protected] 1
Taishan Institute for Hydrogen Biomedicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai’an 271000, China
2
Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai’an 271000, China
3
Departments of Neuroscience and Behavioral Medicine and Psychiatry, Rockefeller Neurosciences Institute, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA
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 characterized by cognitive dysfunction. The potential mechanisms involved in the neuroprotective effect of H2 are also analyzed. Keywords Molecular hydrogen (H2) Neurological disease Neuroprotection Anti-oxidation Anti-inflammation Anti-apoptosis
Introduction Molecular hydrogen (H2) was first discovered by the chemist Henry Cavendish in 1766. It is a colorless, odorless, and physiologically inert gas. The biological functions of H2 were gradually confirmed by scientists in the late 20th century. In 1975, Dole [1] discovered that hyperbaric H2 (2.5% O2 and 97.5% H2) causes regression of squamous cell carcinoma in hairless albino mice. He hypothesized that the effect of H2 might be attributed to its ability to scavenge the most damaging oxidant hydroxyl radical (OH). In 2001, Gharib [2] found that 0.7 MPa H2 has an anti-inflammatory effect on the chronic liver inflammation associated with schis
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