# Hydrogen Gas Alleviates Sepsis-Induced Brain Injury by Improving Mitochondrial Biogenesis Through the Activation of PGC-α in Mice.
> 水素ガス吸入がPGC-1α活性化を介したミトコンドリア生合成の改善によりマウスの敗血症関連脳症を軽減する


## Abstract

Sepsis-associated encephalopathy (SAE) develops in roughly one-third of septic patients, yet effective countermeasures remain scarce. Using a cecal ligation and puncture mouse model, this study examined whether 2% H2 gas inhalation (1 h sessions beginning at 1 h and 6 h post-surgery) could mitigate brain injury. Outcomes included 7-day survival, Y-maze cognitive performance, hippocampal CA1 histology (Nissl and TUNEL staining), mitochondrial membrane potential, ATP levels, respiratory chain complex I and II activities, and protein expression of PGC-1α, NRF2, and Tfam. H2-treated mice showed improved survival, better cognitive scores, and enhanced mitochondrial function alongside upregulated biogenesis markers. Co-administration of the PGC-1α inhibitor SR-18292 reversed these improvements, indicating that PGC-1α-driven mitochondrial biogenesis is central to the neuroprotective action of hydrogen gas in septic mice.

### Mechanism

H2 gas activates PGC-1α, which in turn upregulates NRF2 and Tfam, promoting mitochondrial biogenesis and thereby restoring mitochondrial membrane potential, ATP production, and complex I activity while reducing apoptosis in the septic brain.

## Bibliographic

- **Authors**: Xie K, Yin L, Wang Y, Chen H, Mao X, Wang G
- **Journal**: Shock
- **Year**: 2021 (2021-01-01)
- **PMID**: [32590694](https://pubmed.ncbi.nlm.nih.gov/32590694/)
- **DOI**: [10.1097/SHK.0000000000001594](https://doi.org/10.1097/SHK.0000000000001594)
- **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 32590694. https://h2-papers.org/en/papers/32590694
> **Source**: PubMed PMID [32590694](https://pubmed.ncbi.nlm.nih.gov/32590694/)