287 - Hydrogen gas inhalation promotes neuroprotection and upregulates ATF5 expression in neonatal hypoxicischemic brain injury

Publication Number: 4282.287

Hideo Jinnou, Aichi Medical University Hospital, Nagakute, Aichi, Japan; Shinji Nakamura, Kagawa university, Kidagun, Kagawa, Japan; Yasuhisa Nakamura, Department of Pediatrics, Nagoya City University West Medical Center, Nagoya, Aichi, Japan; Takashi Kusaka, Kagawa University, takamatsu, Kagawa, Japan

Background: Neonatal hypoxia-ischemic（HI）brain injury leads to cortical and white matter damages, resulting in severe neurological disabilities. Although therapeutic hypothermia is the only clinical intervention, its effectiveness and application is limited. Molecular hydrogen（H2）gas has shown neuroprotective effects through its antioxidant properties, gaining attention as a potential therapeutic strategy. However, its cellular and molecular effects are not well elucidated.

Objective: This study aimed to investigate the cell-type specific impact of H2 gas after neonatal HI injury and to identify underlying molecular mediators of its neuroprotective effects.

Design/Methods: Using a HI brain injury model of neonatal piglets, a powerful preclinical model whose brain resembles that of human neonates in structure and development, we administered 2％ H2 gas for 6 or 24 hours after HI insult. Histological analyses and RNAscope were performed.

Results: H2 gas 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 and myelin loss. RNAscope analyses showed that H2 gas upregulated the expression of the anti-apoptotic factor ATF5 in both neurons and oligodendrocytes.

Conclusion(s): Our study demonstrates that H2 gas exerts robust neuroprotection on cortical neurons and white matter oligodendrocytes after neonatal HI injury, and identifies ATF5 as a potential mediator of its antiapoptotic effects.