# Molecular hydrogen affords neuroprotection in a translational piglet model of hypoxic-ischemic encephalopathy.
> 低酸素性虚血性脳症の翻訳的ブタモデルにおける分子状水素の神経保護効果


## Abstract

A clinically relevant piglet model of perinatal asphyxia (PA) and hypoxic-ischemic encephalopathy (HIE) was developed, incorporating severe hypercapnia alongside hypoxia. Anesthetized, artificially ventilated piglets underwent 20 minutes of asphyxia induced by a 6% O₂ / 20% CO₂ gas mixture, producing profound hypoxia (pO₂ = 27 ± 4 mmHg), combined acidosis (pH = 6.76 ± 0.04), and markedly suppressed electroencephalography (EEG). Following asphyxia, animals were reventilated with either air or 2.1% H₂-enriched air for 4 hours. At 24-hour survival, brains were assessed neuropathologically. H₂-treated animals showed significantly better neuronal preservation in the cerebral cortex, hippocampus, basal ganglia, and thalamus, along with enhanced EEG recovery. Attenuation of 8-hydroxy-2'-deoxyguanosine immunostaining indicated reduced oxidative DNA damage in the H₂ group. These findings support the feasibility of hydrogen gas post-conditioning as a neuroprotective strategy in neonatal asphyxia.

### Mechanism

H₂ inhalation reduced oxidative DNA damage, evidenced by decreased 8-hydroxy-2'-deoxyguanosine immunostaining, thereby attenuating neuronal cell death in cortical and subcortical regions following hypoxic-ischemic injury.

## Bibliographic

- **Authors**: Nemeth J, Toth-Szuki V, Varga V, Kovacs V, Remzso G, Domoki F
- **Journal**: J Physiol Pharmacol
- **Year**: 2016
- **PMID**: [28011948](https://pubmed.ncbi.nlm.nih.gov/28011948/)
- **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 28011948. https://h2-papers.org/en/papers/28011948
> **Source**: PubMed PMID [28011948](https://pubmed.ncbi.nlm.nih.gov/28011948/)