# 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


## 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](https://pubmed.ncbi.nlm.nih.gov/25251596/)
- **DOI**: [10.1016/j.brainres.2014.09.030](https://doi.org/10.1016/j.brainres.2014.09.030)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 2%

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 25251596. https://h2-papers.org/en/papers/25251596
> **Source**: PubMed PMID [25251596](https://pubmed.ncbi.nlm.nih.gov/25251596/)