H₂ Papers

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Hydrogen gas inhalation alleviated cerebral ischemia/reperfusion injury by regulating mitophagy in SH-SY5Y cells and mice via PTEN-induced kinase 1/Parkin pathway.

水素ガス吸入によるPINK1/Parkin経路を介したミトファジー調節と脳虚血再灌流障害の軽減：SH-SY5Y細胞およびマウスを用いた検討

animal study inhalation positive

Abstract

This study examined the effects of molecular hydrogen (H₂) inhalation on cerebral ischemia-reperfusion injury (CIRI) using both a mouse middle cerebral artery occlusion/reperfusion (MCAO/R) model and human neuroblastoma SH-SY5Y cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). In vivo, H₂ inhalation reduced infarct volume, improved neurological deficit scores, decreased histopathological damage, and suppressed neuronal apoptosis while promoting mitophagy. In OGD/R-exposed SH-SY5Y cells, H₂ enhanced cell viability, lowered mitochondrial reactive oxygen species, preserved mitochondrial membrane potential, and activated the PINK1/Parkin mitophagy pathway. Concurrently, the Nrf2/HO-1 antioxidant axis was upregulated and NF-κB-driven inflammatory signaling was attenuated. Pretreatment with the Nrf2-specific inhibitor ML385 (5 μM) substantially reversed these mitochondrial protective and anti-apoptotic outcomes, indicating that Nrf2 activation is integral to H₂-mediated neuroprotection against CIRI.

Mechanism

H₂ activates the PINK1/Parkin pathway to promote selective clearance of damaged mitochondria (mitophagy), upregulates the Nrf2/HO-1 antioxidant axis, and suppresses NF-κB inflammatory signaling, collectively reducing oxidative stress and neuronal apoptosis in ischemia-reperfusion conditions.

Bibliographic

Authors
Wang Z, Feng WB, Zhou J, Huang L, Fang C, Yuan J, et al.
Journal
J Stroke Cerebrovasc Dis
Year
2026 (2026-04-26)
PMID
42049119
DOI
10.1016/j.jstrokecerebrovasdis.2026.108645

Tags

Disease:ischemia-reperfusion injury (107) stroke / cerebral ischemia (31) Mechanism:apoptosis regulation (280) autophagy (32) mitochondrial function (226) Nrf2 pathway (106) oxidative stress (899) reactive oxygen species (774)

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.

→ Evidence by delivery route

Safety notes

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.

See also:

Other papers on the same disease / condition