# Hydrogen-induced Neuroprotection in Neonatal Hypoxic-ischemic Encephalopathy.
> 新生児低酸素性虚血性脳症における水素誘発性神経保護作用のレビュー


## Abstract

Hypoxic-ischemic encephalopathy (HIE) is a leading contributor to neonatal morbidity, mortality, and long-term neurodevelopmental impairment in term infants. This review evaluates preclinical investigations using molecular hydrogen in rodent and piglet HIE models. Across virtually all model species and insult types examined, hydrogen consistently preserved neurovascular integrity, neuronal viability, and neurocognitive performance. In most studies, hydrogen administration commenced after the hypoxic-ischemic event, strengthening the translational relevance of the findings. The predominant mechanisms identified include antioxidant activity, suppression of apoptosis, and attenuation of inflammatory responses. Whole-body hypothermia remains the established standard for reducing HIE-associated disability, yet complementary approaches are still needed. Notably, a combined neuroprotective benefit of hydrogen alongside hypothermia has not yet been demonstrated experimentally, and such studies are considered necessary before clinical evaluation of hydrogen as an adjunct neuroprotective intervention in HIE can proceed.

### Mechanism

Molecular hydrogen is proposed to confer neuroprotection through antioxidant scavenging of reactive oxygen species, inhibition of apoptotic pathways, and suppression of neuroinflammation, collectively preserving neurovascular function and neuronal survival following hypoxic-ischemic insult.

## Bibliographic

- **Authors**: Domoki F
- **Journal**: Curr Pharm Des
- **Year**: 2021
- **PMID**: [33185158](https://pubmed.ncbi.nlm.nih.gov/33185158/)
- **DOI**: [10.2174/1381612826666201113095720](https://doi.org/10.2174/1381612826666201113095720)
- **Study type**: review
- **Delivery route**: mixed routes
- **Effect reported**: positive

## Delivery context

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident 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)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 33185158. https://h2-papers.org/en/papers/33185158
> **Source**: PubMed PMID [33185158](https://pubmed.ncbi.nlm.nih.gov/33185158/)