# Molecular hydrogen alleviates brain injury and cognitive impairment in a chronic sequelae model of murine polymicrobial sepsis.
> 慢性敗血症後遺症モデルマウスにおける分子状水素の脳損傷および認知機能障害に対する保護効果


## Abstract

Sepsis-associated encephalopathy (SAE) is linked to severe brain damage and prolonged cognitive decline. Male C57BL/6J mice received intraperitoneal injections of human fecal suspension to establish a chronic SAE model. Hydrogen gas at 2% concentration was administered via inhalation for 60 minutes at 1 and 6 hours post-induction. Compared with untreated SAE animals, hydrogen-inhaling mice showed higher 14-day survival rates and better performance in the Morris Water Maze (days 8–14). Histological analysis revealed reduced hippocampal neuronal damage, while Evans blue extravasation and brain water content were both diminished. Inflammatory mediators including TNF-α, IL-6, and HMGB1 were suppressed, and tight junction proteins ZO-1 and Occludin were better preserved. Nrf2 and HO-1 protein levels were modulated, suggesting engagement of antioxidant pathways. These findings indicate that 2% H2 inhalation attenuates oxidative stress, neuroinflammation, and blood-brain barrier disruption in septic mice.

### Mechanism

Inhalation of 2% H2 activates the Nrf2/HO-1 antioxidant pathway, suppresses pro-inflammatory cytokines (TNF-α, IL-6, HMGB1), and preserves tight junction proteins ZO-1 and Occludin, thereby limiting blood-brain barrier disruption in septic mice.

## Bibliographic

- **Authors**: Jiang Y, Zhang K, Wang Y, Lian N, Xie K, Yu Y
- **Journal**: Exp Brain Res
- **Year**: 2020
- **PMID**: [33052428](https://pubmed.ncbi.nlm.nih.gov/33052428/)
- **DOI**: [10.1007/s00221-020-05950-4](https://doi.org/10.1007/s00221-020-05950-4)
- **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 33052428. https://h2-papers.org/en/papers/33052428
> **Source**: PubMed PMID [33052428](https://pubmed.ncbi.nlm.nih.gov/33052428/)