# Coadministration of hydrogen gas as part of the carrier gas mixture suppresses neuronal apoptosis and subsequent behavioral deficits caused by neonatal exposure to sevoflurane in mice.
> 新生仔マウスにおけるセボフルラン麻酔誘発性神経アポトーシスおよび行動障害に対する水素ガス併用吸入の抑制効果


## Abstract

Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 hours, with or without concurrent administration of hydrogen gas (< 1.3%) mixed into the carrier gas. Western blot analysis of cleaved caspase-3 and cleaved PARP demonstrated that hydrogen co-administration reduced neuronal apoptosis to approximately 40% of the level observed with sevoflurane alone (P < 0.001). Immunohistochemical staining for 4-hydroxy-2-nonenal indicated that oxidative stress induced by neonatal sevoflurane exposure was markedly attenuated in the hydrogen group. Behavioral assessments in adulthood, including fear conditioning and sociability tests, revealed that animals receiving hydrogen alongside sevoflurane did not develop the long-term memory impairment or abnormal social behaviors seen in the sevoflurane-only group. These findings suggest that hydrogen gas inhalation during anesthesia may protect the developing brain from anesthetic-induced oxidative neurotoxicity.

### Mechanism

Sevoflurane-induced mitochondrial dysfunction elevates oxidative stress, triggering neuronal apoptosis via caspase-3 activation. Hydrogen gas is proposed to scavenge reactive oxygen species, thereby reducing 4-hydroxy-2-nonenal accumulation and suppressing the apoptotic cascade in the developing brain.

## Bibliographic

- **Authors**: Yonamine R, Satoh Y, Kodama M, Araki Y, Kazama T
- **Journal**: Anesthesiology
- **Year**: 2013
- **PMID**: [23221861](https://pubmed.ncbi.nlm.nih.gov/23221861/)
- **DOI**: [10.1097/ALN.0b013e318275146d](https://doi.org/10.1097/ALN.0b013e318275146d)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 1.3%

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information 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)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 23221861. https://h2-papers.org/en/papers/23221861
> **Source**: PubMed PMID [23221861](https://pubmed.ncbi.nlm.nih.gov/23221861/)