# Neuroprotective Effects of Molecular Hydrogen via Oxidative Stress and Neuroinflammation Regulation in a 5xFAD Mouse Model.
> 5xFADマウスモデルにおける分子状水素の酸化ストレス・神経炎症調節を介した神経保護効果


## Abstract

Using the 5xFAD transgenic mouse model carrying human APP and PSEN1 mutations, this study examined the effects of daily 2% H2 gas inhalation (1 h/day, 4 weeks) on amyloid-driven neuropathology. H2 exposure reduced hippocampal reactive oxygen species and elevated systemic catalase activity, while hippocampal ATP levels were improved, suggesting enhanced mitochondrial function. In serum, pro-inflammatory cytokines TNF-α and IL-1β declined, whereas IL-10 was restored and IL-13 was partially normalized, indicating a shift toward an anti-inflammatory peripheral milieu. Within the hippocampus, NRF2 was upregulated, NF-κB activation was attenuated, the BAX/BCL-2 apoptotic ratio decreased, NeuN-positive neuronal populations were preserved, and Aβ42 burden was reduced. These results collectively demonstrate that H2 inhalation provides multi-target neuroprotection in this AD model by simultaneously addressing redox imbalance, inflammatory signaling, apoptotic pathways, and amyloid accumulation.

### Mechanism

H2 inhalation activates NRF2 to reduce oxidative stress, suppresses NF-κB-driven neuroinflammation, lowers the BAX/BCL-2 apoptotic ratio, improves mitochondrial ATP production, and decreases hippocampal Aβ42 accumulation, collectively preserving neuronal integrity in amyloid-laden tissue.

## Bibliographic

- **Authors**: Mo C, Bajgai J, Rahman MH, Ma HY, Pham TT, Zhang H, et al.
- **Journal**: Antioxidants (Basel)
- **Year**: 2026 (2026-03-23)
- **PMID**: [41897548](https://pubmed.ncbi.nlm.nih.gov/41897548/)
- **DOI**: [10.3390/antiox15030404](https://doi.org/10.3390/antiox15030404)
- **PMC**: [PMC13024456](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024456/)
- **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 41897548. https://h2-papers.org/en/papers/41897548
> **Source**: PubMed PMID [41897548](https://pubmed.ncbi.nlm.nih.gov/41897548/)