4.6 Article

Molecular Hydrogen: an Emerging Therapeutic Medical Gas for Brain Disorders

Journal

MOLECULAR NEUROBIOLOGY
Volume 60, Issue 4, Pages 1749-1765

Publisher

SPRINGER
DOI: 10.1007/s12035-022-03175-w

Keywords

Hydrogen; Medical gas; Neuroinflammation; Oxidative stress; Alzheimer's disease; Brain disorders

Categories

Funding

  1. National Key Research and Development Program of China [2017YFB0403801]
  2. National Nat-ural Science Foundation of China [31971096, 31771256, 31971099, 32100918]
  3. China Postdoctoral Science Foundation [2021M690060, 2022T150227]
  4. Sigma Xi Grants in Aid of Research (GIAR) program [G03152021115804390]

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Oxidative stress and neuroinflammation play important roles in the development of neurodegenerative disorders and brain injuries. Molecular hydrogen has demonstrated excellent antioxidant and anti-inflammatory effects, making it a promising therapy for various brain disorders. This paper reviews the administration routes, effects, and underlying mechanisms of hydrogen therapy in brain disorders, while also discussing the remaining challenges in its implementation.
Oxidative stress and neuroinflammation are the main physiopathological changes involved in the initiation and progression of various neurodegenerative disorders or brain injuries. Since the landmark finding reported in 2007 found that hydrogen reduced the levels of peroxynitrite anions and hydroxyl free radicals in ischemic stroke, molecular hydrogen's antioxidative and anti-inflammatory effects have aroused widespread interest. Due to its excellent antioxidant and anti-inflammatory properties, hydrogen therapy via different routes of administration exhibits great therapeutic potential for a wide range of brain disorders, including Alzheimer's disease, neonatal hypoxic-ischemic encephalopathy, depression, anxiety, traumatic brain injury, ischemic stroke, Parkinson's disease, and multiple sclerosis. This paper reviews the routes for hydrogen administration, the effects of hydrogen on the previously mentioned brain disorders, and the primary mechanism underlying hydrogen's neuroprotection. Finally, we discuss hydrogen therapy's remaining issues and challenges in brain disorders. We conclude that understanding the exact molecular target, finding novel routes, and determining the optimal dosage for hydrogen administration is critical for future studies and applications.

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