# Optimized dose of hydrogen-enriched water with minocycline combination therapy in experimental ischemic stroke.
> 実験的脳虚血モデルにおける水素富化水の最適用量とミノサイクリン併用による神経保護効果


## Abstract

Using a transient middle cerebral artery occlusion (MCAO) rat model, this study investigated the dose-response relationship of hydrogen-enriched water (3.2 ppm) and assessed whether its combination with minocycline (20 mg/kg) enhances neuroprotection. Sixty-six male and female Sprague-Dawley rats underwent 60-minute MCAO and received hydrogen-enriched water at doses ranging from 5 to 30 mL/kg, alone or alongside minocycline, administered post-reperfusion and on days 1 and 2. At 7 days post-stroke, 20 mL/kg emerged as the optimal dose, yielding the best Garcia neurological scores and smallest infarct volumes, with a quadratic dose-response relationship (R = 0.751 for Garcia scores; R = 0.289 for lesion volume). The dual-agent regimen significantly surpassed hydrogen monotherapy in both functional recovery and infarct reduction, with no sex-based differences detected. These findings support dose-optimized hydrogen-enriched water as a neuroprotective strategy and highlight the additive benefit of combining it with minocycline.

### Mechanism

Hydrogen-enriched water exerts anti-inflammatory and antioxidant effects, while minocycline provides additional neuroprotection; their combination appears to additively reduce infarct volume and improve neurological recovery following ischemia-reperfusion injury.

## Bibliographic

- **Authors**: Jiang Z, Alamuri TT, Yang DL, Annarino T, Muir ER, Duong TQ
- **Journal**: Brain Res
- **Year**: 2025 (2025-11-01)
- **PMID**: [40935311](https://pubmed.ncbi.nlm.nih.gov/40935311/)
- **DOI**: [10.1016/j.brainres.2025.149940](https://doi.org/10.1016/j.brainres.2025.149940)
- **PMC**: [PMC12779082](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779082/)
- **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 40935311. https://h2-papers.org/en/papers/40935311
> **Source**: PubMed PMID [40935311](https://pubmed.ncbi.nlm.nih.gov/40935311/)