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[Protective effects of inhaled hydrogen gas on cognitive function in mice with sepsis-associated encephalopathy].

敗血症関連脳症マウスモデルにおける水素ガス吸入の認知機能保護効果

animal study inhalation positive 2%

Abstract

This animal study examined whether inhaled hydrogen gas (2% H2) could protect cognitive function in male ICR mice subjected to cecal ligation and puncture (CLP)-induced sepsis-associated encephalopathy (SAE). Eighty-four mice were allocated to four groups: sham, sham+H2, sepsis, and sepsis+H2. Hydrogen was administered for 1 hour at 1 and 6 hours post-operation. At 24 hours, CLP mice showed marked neuronal damage in hippocampal CA1, reduced superoxide dismutase (SOD) and catalase (CAT) activities, and elevated malondialdehyde (MDA) and 8-iso-prostaglandin F2α levels in serum and hippocampus. H2 inhalation significantly reversed these changes. Behavioral assessments via Y-maze and fear-conditioning tests conducted from days 3 to 14 revealed that H2-treated septic mice spent more time in novel zones and exhibited higher freezing percentages compared with untreated septic controls. The findings suggest that enhanced antioxidant enzyme activity and reduced oxidative stress markers underlie the neuroprotective effects observed.

Mechanism

H2 inhalation elevated superoxide dismutase and catalase activities while reducing lipid peroxidation markers (MDA and 8-iso-PGF2α) in serum and hippocampus, thereby attenuating neuronal damage in the CA1 region and preserving cognitive function in CLP-induced septic mice.

Bibliographic

Authors
Liu L, Xie K, Chen H, Dong XX, Li Y, Yu Y
Journal
Zhonghua Yi Xue Za Zhi
Year
2014 (2014-11-04)
PMID
25573317

Tags

Disease:cognitive decline (111) sepsis (48) Delivery:inhalation delivery (196) Mechanism:antioxidant enzymes (423) hydroxyl radical scavenging (352) anti-inflammatory (743) lipid peroxidation (238) oxidative stress (899)

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.

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