# Inhalation of hydrogen gas mitigates sevoflurane-induced neuronal apoptosis in the neonatal cortex and is associated with changes in protein phosphorylation.
> 水素ガス吸入による新生児大脳皮質のセボフルラン誘発神経細胞アポトーシス抑制とタンパク質リン酸化変動の関連


## Abstract

Sevoflurane exposure in neonatal mice induces apoptosis in neural progenitor cells of the retrosplenial cortex. Co-administration of 1–8% hydrogen gas for 3 hours reduced caspase-3-mediated apoptotic cell death and attenuated c-Jun phosphorylation along with downstream pathway activation, both of which are driven by oxidative stress. Lipid peroxidation and oxidative DNA damage elevated by anesthesia were also diminished by hydrogen inhalation. Phosphoproteomic profiling identified clusters of differentially phosphorylated proteins in the sevoflurane-exposed neonatal brain, including those involved in neuronal development and synaptic signaling. Hydrogen inhalation altered cellular transport pathways dependent on hyperphosphorylated proteins such as microtubule-associated protein family members, suggesting these changes contribute to the neuroprotective mechanism against anesthetic-induced neuronal cell death.

### Mechanism

Hydrogen gas reduces oxidative stress, suppresses c-Jun phosphorylation and caspase-3-mediated apoptosis, and modifies phosphorylation of cellular transport proteins including microtubule-associated protein family members in the sevoflurane-exposed neonatal brain.

## Bibliographic

- **Authors**: Iketani M, Hatomi M, Fujita Y, Watanabe N, Ito M, Kawaguchi H, et al.
- **Journal**: J Neurochem
- **Year**: 2024
- **PMID**: [38849977](https://pubmed.ncbi.nlm.nih.gov/38849977/)
- **DOI**: [10.1111/jnc.16142](https://doi.org/10.1111/jnc.16142)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 1–8%

## 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 38849977. https://h2-papers.org/en/papers/38849977
> **Source**: PubMed PMID [38849977](https://pubmed.ncbi.nlm.nih.gov/38849977/)