# Hydrogen inhalation inhibits microglia activation and neuroinflammation in a rat model of traumatic brain injury.
> 外傷性脳損傷ラットモデルにおける水素吸入によるミクログリア活性化および神経炎症の抑制


## Abstract

This study examined the neuroprotective potential of hydrogen inhalation (HI) in a rat model of traumatic brain injury (TBI), focusing on optimal intervention timing and underlying mechanisms. Among the protocols tested, administration of 4% H2 gas during the first 24 hours post-TBI yielded the greatest benefit. Histopathological analysis revealed reductions in reactive astrocytosis and microglial activation. Nissl staining showed a significant decline in dark neuron counts at 2 hours post-TBI and attenuated neuronal loss at day 3. Immunohistochemical staining demonstrated decreased CD16-positive cells alongside increased CD206-positive cells, indicating a shift in microglial polarization. Multiplex cytokine profiling revealed pronounced modulation of IL-12, IFN-γ, and GM-CSF levels at 24 hours post-TBI. Collectively, these findings suggest that H2 inhalation exerts neuroprotective effects primarily through suppression of microglial activation and attenuation of neuroinflammation.

### Mechanism

Inhalation of 4% H2 suppresses microglial activation by shifting polarization from pro-inflammatory (CD16-positive) to anti-inflammatory (CD206-positive) phenotypes and reducing cytokine levels including IL-12, IFN-γ, and GM-CSF, thereby attenuating neuroinflammation after TBI.

## Bibliographic

- **Authors**: Zhao Q, Xie F, Guo DZ, Ju FD, He J, Yao TT, et al.
- **Journal**: Brain Res
- **Year**: 2020 (2020-12-01)
- **PMID**: [32814064](https://pubmed.ncbi.nlm.nih.gov/32814064/)
- **DOI**: [10.1016/j.brainres.2020.147053](https://doi.org/10.1016/j.brainres.2020.147053)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 4%

## 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 32814064. https://h2-papers.org/en/papers/32814064
> **Source**: PubMed PMID [32814064](https://pubmed.ncbi.nlm.nih.gov/32814064/)