# Hydrogen alleviates hypoxic-ischaemic brain damage in neonatal rats by inhibiting injury of brain pericytes.
> 水素富化水が新生仔ラットの低酸素虚血性脳損傷における脳周皮細胞障害を抑制するメカニズムの解明


## Abstract

A neonatal hypoxic-ischemic brain damage (HIBD) model was established in 7-day-old Sprague-Dawley rats to investigate the role of hydrogen-rich water (HRW) in protecting cerebrovascular pericytes. Animals received varying HRW doses, and pericyte oxidative stress, cerebrovascular integrity, and brain tissue damage were evaluated. In parallel, cultured pericytes underwent oxygen-glucose deprivation and HRW exposure in vitro. HRW markedly reduced HI-induced oxidative injury in brain pericytes, partly through activation of the Nrf2-HO-1 signaling pathway, which was associated with improved cerebrovascular function and reduced brain damage. Compared with individual inhibitors targeting apoptosis, ferroptosis, parthanatos, necroptosis, or autophagy, HRW demonstrated superior suppression of pericyte death across all these modalities. Hepatic and renal function remained unaffected at the doses tested, supporting a favorable safety profile. These findings clarify the mechanistic basis by which hydrogen influences HIBD from a pericyte-centered perspective.

### Mechanism

HRW activates the Nrf2-HO-1 antioxidant signaling pathway in brain pericytes, reducing oxidative stress and simultaneously suppressing multiple cell death modalities including apoptosis, ferroptosis, parthanatos, necroptosis, and autophagy.

## Bibliographic

- **Authors**: Li H, Sun H, Li SC, Huang L, Zhang MH, Wang SP, et al.
- **Journal**: J Cell Mol Med
- **Year**: 2024
- **PMID**: [39001579](https://pubmed.ncbi.nlm.nih.gov/39001579/)
- **DOI**: [10.1111/jcmm.18505](https://doi.org/10.1111/jcmm.18505)
- **PMC**: [PMC11245570](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245570/)
- **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 39001579. https://h2-papers.org/en/papers/39001579
> **Source**: PubMed PMID [39001579](https://pubmed.ncbi.nlm.nih.gov/39001579/)