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Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis.

盲腸結紮穿刺モデルマウスにおける水素ガス吸入による脳損傷軽減:神経炎症・酸化ストレス・神経細胞アポトーシスへの影響

animal study inhalation positive 2%

Abstract

Using a cecal ligation and puncture (CLP) mouse model of sepsis, this study examined the effects of 2% H2 gas inhalation administered for 60 minutes at 1 and 6 hours post-surgery. H2-treated animals showed markedly improved 7-day survival rates and cognitive performance assessed by Y-maze and fear conditioning tests on days 3, 5, 7, and 14. Hippocampal histopathology, blood-brain barrier permeability, and brain edema were all reduced in H2-treated mice. Inflammatory cytokine levels and oxidative markers (MDA and 8-iso-PGF2α) in serum and hippocampus were decreased, while antioxidant enzyme activities (SOD and CAT) were elevated. Additionally, nuclear translocation of Nrf2 and upregulation of HO-1 expression were observed, suggesting these pathways contribute to the neuroprotective effects of H2 inhalation in sepsis-induced brain injury.

Mechanism

H2 inhalation promotes nuclear translocation of Nrf2 and upregulates HO-1 expression, thereby reducing inflammatory cytokine production, oxidative damage (lowered MDA and 8-iso-PGF2α, elevated SOD and CAT), and neuronal apoptosis in the hippocampus during sepsis.

Bibliographic

Authors
Liu L, Xie K, Chen H, Dong XX, Li Y, Wang G, et al.
Journal
Brain Res
Year
2014 (2014-11-17)
PMID
25251596
DOI
10.1016/j.brainres.2014.09.030

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.

→ 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.

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