# Inhaled Hor CODo Not Augment the Neuroprotective Effect of Therapeutic Hypothermia in a Severe Neonatal Hypoxic-Ischemic Encephalopathy Piglet Model.
> 重症新生児低酸素性虚血性脳症ブタモデルにおける吸入H₂およびCO₂が低体温療法の神経保護効果に与える影響


## Abstract

Using a 48-hour piglet model of severe neonatal hypoxic-ischemic encephalopathy (HIE), this study examined whether 4 hours of 2.1% H2 inhalation or graded CO2 administration following asphyxia could enhance the neuroprotective benefit of therapeutic hypothermia (33.5°C). Asphyxia produced severe hypoxia (pO2 = 19 ± 5 mmHg) and mixed acidosis (pH = 6.79 ± 0.10), confirmed by abnormal cerebral electrical activity and neuropathology. Hypothermia provided significant neuroprotection in the caudate nucleus but minimal protection in the hippocampus, where mRNA levels of apoptosis-inducing factor and caspase-3 rose approximately 10-fold compared to naive animals. Neither H2 nor CO2 augmented hypothermia-induced neuroprotection in any brain region; moreover, CO2 abolished the protective effect of hypothermia in the caudate nucleus. These findings indicate that neither medical gas reinforces hypothermia-based neuroprotection in this HIE model.

### Mechanism

Hippocampal apoptosis-inducing factor and caspase-3 mRNA increased approximately 10-fold after asphyxia under hypothermia, correlating with region-specific neuroprotective failure. H2 did not modulate these apoptotic markers, and CO2 abolished hypothermia-mediated protection in the caudate nucleus.

## Bibliographic

- **Authors**: Kovács V, Remzső G, Tóth-Szűki V, Varga V, Németh J, Domoki F
- **Journal**: Int J Mol Sci
- **Year**: 2020 (2020-09-16)
- **PMID**: [32948011](https://pubmed.ncbi.nlm.nih.gov/32948011/)
- **DOI**: [10.3390/ijms21186801](https://doi.org/10.3390/ijms21186801)
- **PMC**: [PMC7555370](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555370/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: null
- **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 32948011. https://h2-papers.org/en/papers/32948011
> **Source**: PubMed PMID [32948011](https://pubmed.ncbi.nlm.nih.gov/32948011/)