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Hydrogen gas alleviates sepsis-induced neuroinflammation and cognitive impairment through regulation of DNMT1 and DNMT3a-mediated BDNF promoter IV methylation in mice.

水素ガス吸入が敗血症誘発性神経炎症および認知障害に及ぼす影響：DNMT1・DNMT3aを介したBDNFプロモーターIVメチル化調節機序の解明

Abstract

Sepsis-associated encephalopathy (SAE) contributes to both acute and persistent cognitive deficits. Using a cecal ligation and perforation (CLP) model in C57BL/6 mice, this study examined whether 2% hydrogen gas (H2) inhalation influences SAE through epigenetic regulation. H2 inhalation reduced hippocampal pro-inflammatory cytokines (TNF-α, IL-6, HMGB1) and downregulated DNMT1 and DNMT3a expression without affecting DNMT3b. Quantitative methylation analysis revealed hypomethylation at 5 CpG sites within BDNF promoter IV, accompanied by elevated BDNF protein levels. Morris water maze assessments conducted from day 4 to day 10 post-surgery demonstrated shortened escape latency and increased platform crossings in H2-treated septic mice, indicating improved spatial memory. These findings suggest that H2 inhalation modulates hippocampal BDNF expression through DNMT1- and DNMT3a-dependent promoter IV methylation changes, thereby attenuating SAE-related cognitive impairment.

Mechanism

H2 inhalation suppresses DNMT1 and DNMT3a expression in the hippocampus, inducing hypomethylation at five CpG sites of BDNF promoter IV, which elevates BDNF levels and reduces neuroinflammation and cognitive deficits in septic mice.

Bibliographic

Authors

Yu M, Qin C, Li PY, Zhang YJ, Wang Y, Zhang JH, et al.

Journal

Int Immunopharmacol

Year

2021

PMID

33773206

DOI

10.1016/j.intimp.2021.107583

Tags

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

See also:

• Inhalation concentration and LFL / UFL
• Consumer Affairs Agency accident cases
• LFL / UFL terminology
• Inhalation safety threshold lineage

Other papers on the same disease / condition

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• Emerging Trends and Hot Spots in Sepsis-Associated Encephalopathy Research From 2001 to 2021: A Bibliometric Analysis.
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• Hydrogen Gas Alleviates Sepsis-Induced Brain Injury by Improving Mitochondrial Biogenesis Through the Activation of PGC-α in Mice.
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