# Hydrogen gas inhalation improves delayed brain injury by alleviating early brain injury after experimental subarachnoid hemorrhage.
> 水素ガス吸入によるくも膜下出血後の早期脳損傷軽減を介した遅発性脳損傷の改善：ラットモデルを用いた検討


## Abstract

Using a rat SAH combined with unilateral common carotid artery occlusion (UCCAO) model, this study examined whether 1.3% H2 gas inhalation (mixed with 30% oxygen and balanced nitrogen) could reduce both early brain injury (EBI) and delayed brain injury (DBI). Inhalation was administered for 2 hours on day 0 and 30 minutes on day 1 from anesthesia induction. EBI was evaluated via brain edema, S100B expression, and JNK phosphorylation on day 2, with neurological deficits assessed on day 3. Reactive astrogliosis and cerebral vasospasm (CV) severity were measured on days 3 and 7, while DBI was assessed by neurological deficits and neuronal cell death on day 7. Compared with controls, the H2 group showed significant improvements in EBI, reactive astrogliosis, and DBI. CV severity did not differ significantly between groups. These findings indicate that H2 inhalation suppresses DBI by mitigating EBI independently of any effect on cerebral vasospasm.

### Mechanism

H2 is proposed to scavenge reactive oxygen species, thereby suppressing JNK phosphorylation, S100B expression, and brain edema as markers of early brain injury, which in turn reduces reactive astrogliosis and delayed neuronal cell death without altering cerebral vasospasm.

## Bibliographic

- **Authors**: Kumagai K, Toyooka T, Takeuchi S, Otani N, Wada K, Tomiyama A, et al.
- **Journal**: Sci Rep
- **Year**: 2020 (2020-07-23)
- **PMID**: [32704088](https://pubmed.ncbi.nlm.nih.gov/32704088/)
- **DOI**: [10.1038/s41598-020-69028-5](https://doi.org/10.1038/s41598-020-69028-5)
- **PMC**: [PMC7378202](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378202/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 1.3%

## 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 32704088. https://h2-papers.org/en/papers/32704088
> **Source**: PubMed PMID [32704088](https://pubmed.ncbi.nlm.nih.gov/32704088/)