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Hydrogen inhalation inhibits microglia activation and neuroinflammation in a rat model of traumatic brain injury.

外傷性脳損傷ラットモデルにおける水素吸入によるミクログリア活性化および神経炎症の抑制

animal study inhalation positive 4%

Abstract

This study examined the neuroprotective potential of hydrogen inhalation (HI) in a rat model of traumatic brain injury (TBI), focusing on optimal intervention timing and underlying mechanisms. Among the protocols tested, administration of 4% H2 gas during the first 24 hours post-TBI yielded the greatest benefit. Histopathological analysis revealed reductions in reactive astrocytosis and microglial activation. Nissl staining showed a significant decline in dark neuron counts at 2 hours post-TBI and attenuated neuronal loss at day 3. Immunohistochemical staining demonstrated decreased CD16-positive cells alongside increased CD206-positive cells, indicating a shift in microglial polarization. Multiplex cytokine profiling revealed pronounced modulation of IL-12, IFN-γ, and GM-CSF levels at 24 hours post-TBI. Collectively, these findings suggest that H2 inhalation exerts neuroprotective effects primarily through suppression of microglial activation and attenuation of neuroinflammation.

Mechanism

Inhalation of 4% H2 suppresses microglial activation by shifting polarization from pro-inflammatory (CD16-positive) to anti-inflammatory (CD206-positive) phenotypes and reducing cytokine levels including IL-12, IFN-γ, and GM-CSF, thereby attenuating neuroinflammation after TBI.

Bibliographic

Authors
Zhao Q, Xie F, Guo DZ, Ju FD, He J, Yao TT, et al.
Journal
Brain Res
Year
2020 (2020-12-01)
PMID
32814064
DOI
10.1016/j.brainres.2020.147053

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.

→ 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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