# Molecular hydrogen mitigates traumatic brain injury-induced lung injury via NLRP3 inflammasome inhibition.
> 分子状水素はNLRP3インフラマソーム抑制を介して外傷性脳損傷誘発性肺傷害を軽減する


## Abstract

Using a controlled cortical impact mouse model of traumatic brain injury (TBI), this study examined the effects of 2% hydrogen gas inhalation administered for 60 minutes beginning at 1 and 6 hours post-injury. TBI activated pulmonary NLRP3 inflammasome signaling, elevating ASC and caspase-1 expression and increasing secretion of IL-1β and IL-18. Hydrogen inhalation significantly reduced histopathological lung damage, apoptosis (TUNEL assay), wet-to-dry weight ratio, myeloperoxidase activity, and bronchoalveolar lavage fluid protein content. Co-administration of hydrogen with the selective NLRP3 inhibitor MCC950 (10 mg/kg intraperitoneally, 30 minutes before TBI) conferred greater pulmonary protection than either intervention alone, indicating that NLRP3 inflammasome inhibition is a central mechanism underlying hydrogen-mediated attenuation of TBI-induced lung injury.

### Mechanism

Inhaled 2% hydrogen suppresses NLRP3 inflammasome activation in lung tissue, reducing caspase-1 cleavage and downstream secretion of IL-1β and IL-18, thereby attenuating TBI-induced pulmonary inflammation and apoptosis.

## Bibliographic

- **Authors**: Liu L, Wang SP, Jiang L, Wang J, Chen J, Zhang H, et al.
- **Journal**: BMC Chem
- **Year**: 2025 (2025-05-22)
- **PMID**: [40405232](https://pubmed.ncbi.nlm.nih.gov/40405232/)
- **DOI**: [10.1186/s13065-025-01513-2](https://doi.org/10.1186/s13065-025-01513-2)
- **PMC**: [PMC12100871](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100871/)
- **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 40405232. https://h2-papers.org/en/papers/40405232
> **Source**: PubMed PMID [40405232](https://pubmed.ncbi.nlm.nih.gov/40405232/)