# Molecular Hydrogen Affords Similar Neuroprotection to Therapeutic Hypothermia in a Porcine Model of Neonatal Hypoxic-Ischemic Encephalopathy.
> 新生児低酸素性虚血性脳症ブタモデルにおける分子状水素吸入と低体温療法の神経保護効果の比較


## Abstract

Using a translational newborn pig model of hypoxic-ischemic encephalopathy (HIE), piglets underwent 20 minutes of asphyxia via a hypoxic/hypercapnic gas mixture and were then reoxygenated and observed for 48 hours. Animals were randomly allocated to normothermia, continuous 2.1% H2 inhalation, or hypothermia (33.5°C for 37 hours with gradual rewarming) groups. Electroencephalography (EEG), visual evoked potentials (VEPs), and neuropathological assessments were performed. Hypothermia abolished post-asphyxia seizures and shortened VEP latency, whereas H2 inhalation delayed seizure onset and elevated quantitative EEG complexity markers. Neuropathological analysis showed severe thalamic damage in normothermic controls; both H2 and hypothermia significantly reduced this injury. Neocortical, hippocampal, and basal ganglia damage was comparatively mild and unaffected by either intervention. These results indicate that continuous H2 inhalation achieves neuroprotection in the thalamus comparable to hypothermia, while also producing distinct electrophysiological effects.

### Mechanism

Inhaled H2 is thought to reduce oxidative stress and neuroinflammation following hypoxic-ischemic injury, thereby attenuating thalamic neuronal death and preserving electrophysiological signal complexity as reflected in quantitative EEG measures.

## Bibliographic

- **Authors**: Balog E, Remzső G, Tóth-Szűki V, Rózsa É, Kovács V, Domoki F
- **Journal**: Antioxidants (Basel)
- **Year**: 2025 (2025-11-25)
- **PMID**: [41462605](https://pubmed.ncbi.nlm.nih.gov/41462605/)
- **DOI**: [10.3390/antiox14121405](https://doi.org/10.3390/antiox14121405)
- **PMC**: [PMC12729368](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12729368/)
- **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 41462605. https://h2-papers.org/en/papers/41462605
> **Source**: PubMed PMID [41462605](https://pubmed.ncbi.nlm.nih.gov/41462605/)