# Molecular hydrogen alleviates lung injury after traumatic brain injury: Pyroptosis and apoptosis.
> 外傷性脳損傷後の急性肺損傷に対する水素吸入の効果：パイロトーシスおよびアポトーシスへの影響


## Abstract

Acute lung injury (ALI) secondary to traumatic brain injury (TBI) is a life-threatening condition in which inflammatory cascades and programmed cell death are central pathological drivers. Male Sprague-Dawley rats underwent fluid percussion injury and were subsequently exposed to 42% H2 (balanced with 21% O2 and nitrogen) for one hour daily. Animals in the TBI-only group exhibited marked pulmonary edema, elevated lung injury scores, and reduced oxygenation indices. Hydrogen inhalation significantly reduced pyroptosis-associated proteins—Caspase-1, ASC, and Gasdermin-D—alongside the pro-inflammatory cytokines IL-1β and IL-18. Apoptotic markers, including cleaved caspase-3 and the BCL-2/Bax ratio, were also favorably modulated. These findings indicate that high-concentration hydrogen inhalation accelerates endogenous recovery and attenuates both pyroptotic and apoptotic cell death pathways in TBI-induced ALI, suggesting potential utility in ICU settings.

### Mechanism

Inhalation of 42% H2 suppresses pyroptosis by downregulating Caspase-1, ASC, and Gasdermin-D, while simultaneously reducing IL-1β and IL-18 levels and modulating cleaved caspase-3 and BCL-2/Bax to attenuate apoptotic cell death in lung tissue following TBI.

## Bibliographic

- **Authors**: Li TT, Sun T, Wang Y, Wan Q, Li W, Yang W
- **Journal**: Eur J Pharmacol
- **Year**: 2022 (2022-01-05)
- **PMID**: [34883075](https://pubmed.ncbi.nlm.nih.gov/34883075/)
- **DOI**: [10.1016/j.ejphar.2021.174664](https://doi.org/10.1016/j.ejphar.2021.174664)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 42%

## 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 34883075. https://h2-papers.org/en/papers/34883075
> **Source**: PubMed PMID [34883075](https://pubmed.ncbi.nlm.nih.gov/34883075/)