# FoxO1-mediated autophagy plays an important role in the neuroprotective effects of hydrogen in a rat model of vascular dementia.
> 血管性認知症ラットモデルにおける水素の神経保護効果とFoxO1依存性オートファジーの関与


## Abstract

Using a bilateral common carotid artery occlusion (2VO) rat model of vascular dementia (VD), this study examined the effects of hydrogen-rich water (HRW) on cognitive function and neuronal integrity. HRW administration significantly improved spatial learning and memory, and reduced neuronal loss and shrinkage in the hippocampal CA1 region, comparable to donepezil. Apoptosis-related markers showed an elevated Bcl-2/Bax ratio and reduced cleaved caspase-3 expression in the hippocampus. Electron microscopy revealed fewer autophagosomes in HRW-treated animals, accompanied by decreased LC3-II/I ratio and Beclin 1 levels alongside increased p62 expression. The autophagy regulators FoxO1 and Atg7 were also downregulated in HRW-treated rats. Collectively, these findings indicate that FoxO1-mediated autophagy suppression is a central component of the neuroprotective mechanism of molecular hydrogen in chronic cerebral hypoperfusion-induced cognitive impairment.

### Mechanism

HRW downregulates FoxO1 and Atg7 to suppress excessive autophagy, while simultaneously increasing the Bcl-2/Bax ratio and reducing cleaved caspase-3, thereby protecting hippocampal neurons from apoptotic and autophagic cell death in a chronic cerebral hypoperfusion model.

## Bibliographic

- **Authors**: Jiang X, Niu X, Guo Q, Dong Y, Xu J, Yin N, et al.
- **Journal**: Behav Brain Res
- **Year**: 2019 (2019-01-01)
- **PMID**: [29885845](https://pubmed.ncbi.nlm.nih.gov/29885845/)
- **DOI**: [10.1016/j.bbr.2018.05.023](https://doi.org/10.1016/j.bbr.2018.05.023)
- **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 29885845. https://h2-papers.org/en/papers/29885845
> **Source**: PubMed PMID [29885845](https://pubmed.ncbi.nlm.nih.gov/29885845/)