Hydrogen Gas Protects Newborn Brains from Birth Injury Damage
- Authors
- Shinji Nakamura, Yasuhisa Nakamura, Hideo Jinnou, Yasuhiro Nakao, Htun Yinmon, Tsutomu Mitsuie, Kosuke Koyano, Masaki Ueno, Takanori Miki, Kazunobu Sawamoto, Shinji Saitoh, Takashi Kusaka
- Journal
- Experimental Neurology
- Year
- 2025
- DOI
- 10.1016/j.expneurol.2025.115590
- Study Type
- Pig
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- Japan
- Health Condition
- Neonatal Hypoxic-Ischemic Brain Injury
- Body System
- Nervous System
TL;DR
Hydrogen gas protected brain cells in newborns after oxygen deprivation by reducing cell death, inflammation, and myelin damage.
Key Finding
Hydrogen gas treatment significantly reduced brain cell death and preserved cell survival in newborn piglets with hypoxic-ischemic brain injury, with effects mediated through activation of the anti-apoptotic protein ATF5.
Summary
Researchers studied whether hydrogen gas could protect newborn pig brains from damage caused by lack of oxygen and blood flow (hypoxia-ischemia). They found that hydrogen gas treatment reduced brain cell death in two important cell types—neurons and oligodendrocytes (cells that insulate nerve fibers)—and activated a protective protein called ATF5. The treatment also reduced inflammation and preserved the protective coating around nerve fibers.
Practical Takeaway
This animal study suggests hydrogen gas may have neuroprotective potential for newborn brain injury, but it was conducted only in piglets and has not been tested in human infants. Much more research, including human clinical trials, would be needed before any therapeutic claims could be made. The findings are preliminary and should not be interpreted as evidence that hydrogen gas is an effective treatment for neonatal brain injury in humans.
Abstract
Neonatal brain injury, typically caused by hypoxia-ischemia (HI), results in irreversible cortical and white matter damage, leading to severe neurological sequelae. Therapeutic hypothermia, the only available clinical intervention, has limited effectiveness and is not suitable for all patients. Molecular hydrogen gas exerts neuroprotective effects due to its antioxidant properties and is gaining attention as a potential therapeutic strategy. However, its cellular and molecular effects in the injured neonatal brain are poorly understood. Using a robust HI brain injury model in neonatal piglets, whose brain structure and development closely resemble those of human neonates, we investigated the cell type-specific impact of hydrogen gas following neonatal HI injury and examined the potential molecular mediators underlying its neuroprotective effects. Hydrogen gas treatment significantly attenuated HI-induced apoptosis in both cortical neurons and white matter oligodendrocytes, thereby preserving their cell densities to levels comparable to uninjured controls. These neuroprotective effects were accompanied by reduced microglial activation, astrocyte expansion and myelin loss. RNAscope analyses revealed that hydrogen gas upregulated the expression of the anti-apoptotic factor activating transcription factor 5 (ATF5) in both neurons and mature oligodendrocytes, suggesting a cell-specific protective mechanism. These findings demonstrate that hydrogen gas exerts robust neuroprotection for cortical neurons and white matter oligodendrocytes following neonatal HI injury, and ATF5 is a potential mediator of its anti-apoptotic effects. Our study highlights the clinical feasibility of hydrogen gas as a novel therapeutic strategy for neonatal brain injury.