# Circulating messenger for neuroprotection induced by molecular hydrogen.
> 分子状水素による神経保護における循環性メッセンジャーの役割


## Abstract

Molecular hydrogen (H₂) exerts protective effects against a range of oxidative-stress-associated conditions. Beyond its well-characterized direct antioxidant action—namely scavenging of the highly cytotoxic hydroxyl radical (•OH)—evidence indicates that neuroprotection persists even after H₂ is no longer present in the body following chronic administration via drinking water, pointing to indirect signaling mechanisms. In a Parkinson's disease mouse model, approximately 7 days of H₂-water preconditioning produced significant neuroprotection. Mechanistic investigations revealed that H₂ in drinking water stimulates ghrelin production and secretion from the stomach through β1-adrenergic receptor activation. The released ghrelin enters systemic circulation, crosses the blood-brain barrier, and activates the growth-hormone secretagogue receptor in the brain. Upregulation of ghrelin mRNA was also confirmed in the ghrelin-producing cell line SG-1. These findings illuminate the chronic, indirect actions of H₂ and suggest avenues for preventive investigation.

### Mechanism

H₂ in drinking water stimulates gastric ghrelin release via β1-adrenergic receptor activation; circulating ghrelin crosses the blood-brain barrier and activates the growth-hormone secretagogue receptor, mediating indirect neuroprotection.

## Bibliographic

- **Authors**: Noda M, Uemura Y, Yoshii Y, Horita T, Takemi S, Sakata I, et al.
- **Journal**: Can J Physiol Pharmacol
- **Year**: 2019
- **PMID**: [31100203](https://pubmed.ncbi.nlm.nih.gov/31100203/)
- **DOI**: [10.1139/cjpp-2019-0098](https://doi.org/10.1139/cjpp-2019-0098)
- **Study type**: review
- **Delivery route**: hydrogen-rich water
- **Effect reported**: not assessed

## 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 31100203. https://h2-papers.org/en/papers/31100203
> **Source**: PubMed PMID [31100203](https://pubmed.ncbi.nlm.nih.gov/31100203/)