4.6 Review

Hydrogen and therapeutic gases for neonatal hypoxic-ischemic encephalopathy: potential neuroprotective adjuncts in translational research

Journal

PEDIATRIC RESEARCH
Volume 89, Issue 4, Pages 753-759

Publisher

SPRINGERNATURE
DOI: 10.1038/s41390-020-0998-z

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Funding

  1. Japan Society for the Promotion of Science [16K10092, 19K08253, 16H06276, 16K19685, 15KK0311]
  2. Kagawa University Faculty of Medicine School of Medicine Alumni Association Sanjukai Research Aid [R1-1, 25-2]
  3. Honjo International Scholarship Foundation
  4. Grants-in-Aid for Scientific Research [19K08253, 15KK0311, 16K10092, 16K19685] Funding Source: KAKEN

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This article summarizes the current research on the use of hydrogen as a neuroprotective agent in the treatment of neurological disorders, especially in the context of hypoxic-ischemic encephalopathy in newborns. Studies have shown that hydrogen has neuroprotective effects in adult diseases, but research in pediatric and neonatal medicine is still limited.
Numerous studies have examined the potential use of therapeutic gases for the treatment of various neurological disorders. Hydrogen gas, a promising neuroprotective agent, has been a focus of study due to its potent antioxidative properties. In translational research into adult diseases, hydrogen has been shown to be neuroprotective in disorders such as cerebral ischemia and traumatic brain injury, and in neurodegenerative diseases such as Alzheimer's disease. Animal and human studies have verified the safety and feasibility of molecular hydrogen. However, despite extensive research on its efficacy in adults, only a few studies have investigated its application in pediatric and neonatal medicine. Neonatal hypoxic-ischemic encephalopathy (HIE) is characterized by damage to neurons and other cells of the nervous system. One of the major contributing factors is excessive exposure to oxidative stress. Current research interest in HIE is shifting toward new neuroprotective agents, as single agents or as adjuncts to therapeutic hypothermia. Here, we review therapeutic gases, particularly hydrogen, and their potentials and limitations in the treatment of HIE in newborns. Impact Translational animal models of neonatal HIE are a current focus of research into the therapeutic usefulness of various gases. Hydrogen ventilation as a single agent or in combination with therapeutic hypothermia shows short- and long-term neuroprotection in neonatal translational HIE models. The optimal target severity for therapeutic interventions should be well established to improve outcomes.

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