H₂ Papers

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Molecular hydrogen inhalation attenuates postoperative cognitive impairment in rats.

水素ガス吸入による術後認知機能障害の軽減：ラットモデルを用いた検討

animal study inhalation positive 2%

Abstract

Using a rat tibial fracture surgery model under anesthesia, this study examined whether 2% H2 inhalation for 3 hours (starting 1 hour post-surgery) could mitigate postoperative cognitive dysfunction. Cognitive assessments via fear conditioning and Y-maze tests on days 1, 3, and 7 revealed significant impairment in surgery-only animals, which was substantially reversed by H2 inhalation. Biochemical analyses showed that H2 suppressed elevated levels of proinflammatory cytokines—TNF-α, IL-1β, IL-6, and HMGB1—in both serum and hippocampal tissue. Additionally, blood-brain barrier integrity was better preserved and hippocampal caspase-3 activity was reduced in H2-treated animals. The findings indicate that modulation of inflammatory signaling and apoptotic pathways underlies the neuroprotective effects of inhaled H2 in this surgical context.

Mechanism

Inhaled H2 suppresses proinflammatory cytokines (TNF-α, IL-1β, IL-6, HMGB1) in serum and hippocampus, reduces caspase-3-mediated apoptosis, and preserves blood-brain barrier integrity, collectively attenuating surgery-induced cognitive decline.

Bibliographic

Authors
Xin Y, Liu H, Zhang P, Chang L, Xie K
Journal
Neuroreport
Year
2017 (2017-08-02)
PMID
28614179
DOI
10.1097/WNR.0000000000000824

Tags

Disease:cognitive decline (111) 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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