H₂ Papers

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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

animal study inhalation positive 2.1%

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

Tags

Disease:ischemia-reperfusion injury (107) Delivery:inhalation delivery (196) Mechanism:apoptosis regulation (280) hydroxyl radical scavenging (352) anti-inflammatory (743) oxidative stress (899) reactive oxygen species (774)

Delivery context

In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.

→ Evidence by delivery route

Safety notes

In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.

See also:

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