# Molecular hydrogen alleviates asphyxia-induced neuronal cyclooxygenase-2 expression in newborn pigs.
> 新生仔ブタにおける窒息誘発性神経細胞COX-2発現に対する分子状水素の抑制効果


## Abstract

Using a neonatal piglet model of hypoxic-ischemic encephalopathy (HIE), this study examined whether asphyxia induces neuronal cyclooxygenase-2 (COX-2) and whether H2 inhalation modifies this response. Piglets underwent either 8 or 20 minutes of asphyxia, followed by inhalation of room air containing 2.1% H2 for 4 hours. Immunohistochemical analysis at 24 hours post-asphyxia revealed that severe HIE produced region-specific increases in COX-2-positive neurons within the parietal and occipital cortices and the CA3 hippocampal subfield. H2 inhalation substantially prevented these elevations. In the parietal cortex, reduced 8-hydroxy-2'-deoxyguanosine immunoreactivity and preserved microglial ramification index accompanied the attenuation of COX-2 induction, indicating concurrent reductions in oxidative stress and neuroinflammation. These findings establish that asphyxia elevates neuronal COX-2 in a region-dependent manner, and that H2 inhalation suppresses this pathway, potentially contributing to its neuroprotective properties.

### Mechanism

H2 inhalation appears to suppress asphyxia-induced neuronal COX-2 upregulation by reducing oxidative stress (evidenced by decreased 8-OHdG immunoreactivity) and attenuating neuroinflammation (reflected by preserved microglial ramification), thereby limiting region-specific brain lesion progression in HIE.

## Bibliographic

- **Authors**: Varga V, Németh J, Oláh O, Tóth-Szűki V, Kovács V, Remzső G, et al.
- **Journal**: Acta Pharmacol Sin
- **Year**: 2018
- **PMID**: [29565041](https://pubmed.ncbi.nlm.nih.gov/29565041/)
- **DOI**: [10.1038/aps.2017.148](https://doi.org/10.1038/aps.2017.148)
- **PMC**: [PMC6289359](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289359/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 2.1%

## 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 29565041. https://h2-papers.org/en/papers/29565041
> **Source**: PubMed PMID [29565041](https://pubmed.ncbi.nlm.nih.gov/29565041/)