# Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice.
> 水素水の継続摂取による慢性拘束ストレスマウスの海馬依存性学習障害の予防効果


## Abstract

In a mouse model of chronic physical restraint stress, brain oxidative stress markers—malondialdehyde and 4-hydroxy-2-nonenal—were significantly elevated, and cognitive performance deteriorated across three behavioral paradigms: passive avoidance learning, novel object recognition, and the Morris water maze. Ad libitum consumption of hydrogen-rich water throughout the restraint period suppressed the rise in oxidative stress markers and fully prevented the observed cognitive deficits in all three tasks. Neuronal proliferation in the hippocampal dentate gyrus, assessed by BrdU incorporation and Ki-67 immunostaining, was reduced by restraint stress but partially restored by hydrogen water intake. No enhancement of cognitive function was detected in non-stressed animals given hydrogen water. These findings indicate that sustained hydrogen water consumption attenuates brain oxidative stress and protects against stress-induced deterioration of learning and memory.

### Mechanism

Hydrogen-rich water selectively scavenges reactive oxygen species in the brain, suppressing accumulation of lipid peroxidation markers (MDA and 4-HNE), thereby preserving hippocampal neurogenesis in the dentate gyrus and preventing stress-induced cognitive decline.

## Bibliographic

- **Authors**: Nagata K, Nakashima-Kamimura N, Mikami T, Ohsawa I, Ohta S
- **Journal**: Neuropsychopharmacology
- **Year**: 2009
- **PMID**: [18563058](https://pubmed.ncbi.nlm.nih.gov/18563058/)
- **DOI**: [10.1038/npp.2008.95](https://doi.org/10.1038/npp.2008.95)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident 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)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 18563058. https://h2-papers.org/en/papers/18563058
> **Source**: PubMed PMID [18563058](https://pubmed.ncbi.nlm.nih.gov/18563058/)