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Molecular hydrogen mitigates traumatic brain injury-induced lung injury via NLRP3 inflammasome inhibition.

分子状水素はNLRP3インフラマソーム抑制を介して外傷性脳損傷誘発性肺傷害を軽減する

animal study inhalation positive 2%

Abstract

Using a controlled cortical impact mouse model of traumatic brain injury (TBI), this study examined the effects of 2% hydrogen gas inhalation administered for 60 minutes beginning at 1 and 6 hours post-injury. TBI activated pulmonary NLRP3 inflammasome signaling, elevating ASC and caspase-1 expression and increasing secretion of IL-1β and IL-18. Hydrogen inhalation significantly reduced histopathological lung damage, apoptosis (TUNEL assay), wet-to-dry weight ratio, myeloperoxidase activity, and bronchoalveolar lavage fluid protein content. Co-administration of hydrogen with the selective NLRP3 inhibitor MCC950 (10 mg/kg intraperitoneally, 30 minutes before TBI) conferred greater pulmonary protection than either intervention alone, indicating that NLRP3 inflammasome inhibition is a central mechanism underlying hydrogen-mediated attenuation of TBI-induced lung injury.

Mechanism

Inhaled 2% hydrogen suppresses NLRP3 inflammasome activation in lung tissue, reducing caspase-1 cleavage and downstream secretion of IL-1β and IL-18, thereby attenuating TBI-induced pulmonary inflammation and apoptosis.

Bibliographic

Authors
Liu L, Wang SP, Jiang L, Wang J, Chen J, Zhang H, et al.
Journal
BMC Chem
Year
2025 (2025-05-22)
PMID
40405232
DOI
10.1186/s13065-025-01513-2
PMC
PMC12100871

Tags

Disease:spinal cord injury (13) Delivery:inhalation delivery (196) Mechanism:apoptosis regulation (280) immune modulation (180) 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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