# Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice.
> 水素水の慢性摂取がLPS誘発性神経炎症および病態行動からの回復に与える影響：マウスモデルによる検討


## Abstract

This study examined whether chronic ad libitum intake of hydrogen-enriched electrochemically reduced water (H-ERW) influences the course of lipopolysaccharide (LPS)-induced neuroinflammation in C57Bl/6 mice. Animals received H-ERW for 7 days before a single intraperitoneal injection of LPS (0.33 mg/kg). Sickness behavior was evaluated 2 hours post-injection, and spontaneous locomotor activity was monitored for 72 hours. Real-time PCR analysis of hippocampal tissue revealed that H-ERW shifted baseline cytokine expression toward an anti-inflammatory profile, characterized by reduced TNF-α and elevated IL-10. Although the peak amplitude of neuroinflammation was increased, its duration was shortened and resolution was accelerated. Parallel experiments in BV-2 immortalized murine microglia reproduced these gene expression changes, implicating microglial modulation as a contributing mechanism. The findings indicate that cytokine expression regulation represents an important mechanism beyond free-radical scavenging through which molecular hydrogen exerts its neuroprotective actions.

### Mechanism

H2 shifts hippocampal cytokine expression toward an anti-inflammatory profile by downregulating TNF-α and upregulating IL-10, while modulating microglial activation in BV-2 cells, thereby shortening the duration of LPS-induced neuroinflammation.

## Bibliographic

- **Authors**: Spulber S, Edoff K, Hong L, Morisawa S, Shirahata S, Ceccatelli S
- **Journal**: PLoS One
- **Year**: 2012
- **PMID**: [22860058](https://pubmed.ncbi.nlm.nih.gov/22860058/)
- **DOI**: [10.1371/journal.pone.0042078](https://doi.org/10.1371/journal.pone.0042078)
- **PMC**: [PMC3409143](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409143/)
- **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 22860058. https://h2-papers.org/en/papers/22860058
> **Source**: PubMed PMID [22860058](https://pubmed.ncbi.nlm.nih.gov/22860058/)