Molecular hydrogen alleviates brain injury and cognitive impairment in a chronic sequelae model of murine polymicrobial sepsis.
慢性敗血症後遺症モデルマウスにおける分子状水素の脳損傷および認知機能障害に対する保護効果
Abstract
Sepsis-associated encephalopathy (SAE) is linked to severe brain damage and prolonged cognitive decline. Male C57BL/6J mice received intraperitoneal injections of human fecal suspension to establish a chronic SAE model. Hydrogen gas at 2% concentration was administered via inhalation for 60 minutes at 1 and 6 hours post-induction. Compared with untreated SAE animals, hydrogen-inhaling mice showed higher 14-day survival rates and better performance in the Morris Water Maze (days 8–14). Histological analysis revealed reduced hippocampal neuronal damage, while Evans blue extravasation and brain water content were both diminished. Inflammatory mediators including TNF-α, IL-6, and HMGB1 were suppressed, and tight junction proteins ZO-1 and Occludin were better preserved. Nrf2 and HO-1 protein levels were modulated, suggesting engagement of antioxidant pathways. These findings indicate that 2% H2 inhalation attenuates oxidative stress, neuroinflammation, and blood-brain barrier disruption in septic mice.
Mechanism
Inhalation of 2% H2 activates the Nrf2/HO-1 antioxidant pathway, suppresses pro-inflammatory cytokines (TNF-α, IL-6, HMGB1), and preserves tight junction proteins ZO-1 and Occludin, thereby limiting blood-brain barrier disruption in septic mice.
Bibliographic
- Authors
- Jiang Y, Zhang K, Wang Y, Lian N, Xie K, Yu Y
- Journal
- Exp Brain Res
- Year
- 2020
- PMID
- 33052428
- DOI
- 10.1007/s00221-020-05950-4
Tags
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.
Safety notes
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