Hydrogen gas promotes neuroprotection and upregulates ATF5 expression in neonatal hypoxic-ischemic brain injury.
新生児低酸素虚血性脳損傷における水素ガスの神経保護効果とATF5発現上昇
Abstract
Using neonatal piglets—whose brain architecture closely parallels that of human newborns—this study examined cell-type-specific responses to hydrogen gas following hypoxic-ischemic (HI) brain injury. Hydrogen gas administration markedly reduced HI-induced apoptosis in cortical neurons and white matter oligodendrocytes, maintaining cell densities comparable to uninjured controls. Concurrently, microglial activation, astrocyte proliferation, and myelin loss were all diminished. RNAscope analysis demonstrated that hydrogen gas elevated expression of the anti-apoptotic transcription factor ATF5 in both neurons and mature oligodendrocytes, pointing to a cell-specific protective mechanism. These results identify ATF5 as a candidate molecular mediator of hydrogen gas-mediated neuroprotection in the neonatal HI setting.
Mechanism
Hydrogen gas upregulates the anti-apoptotic transcription factor ATF5 in cortical neurons and mature oligodendrocytes, suppressing hypoxia-ischemia-induced apoptosis and thereby preserving cell density in neonatal brain tissue.
Bibliographic
- Authors
- Nakamura S, Nakamura Y, Jinnou H, Nakao Y, Yinmon H, Mitsuie T, et al.
- Journal
- Exp Neurol
- Year
- 2026
- PMID
- 41386344
- DOI
- 10.1016/j.expneurol.2025.115590
Tags
Delivery context
In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.
Safety notes
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