Chronic molecular hydrogen inhalation mitigates short and long-term memory loss in polymicrobial sepsis.

Abstract

Sepsis rapidly affects the central nervous system through circulating inflammatory mediators that penetrate the hippocampus and prefrontal cortex, inducing neuroinflammation and subsequent memory deficits. Using a polymicrobial sepsis animal model, this study examined whether chronic molecular hydrogen inhalation could mitigate both short- and long-term memory impairment. Behavioral assessments demonstrated that chronic H2 exposure reduced sepsis-associated memory loss. Additionally, acute H2 inhalation lowered neuroinflammatory markers in memory-relevant brain regions and elevated total Nrf2 protein levels—a transcription factor governing a broad array of antioxidant and anti-inflammatory gene expressions. These findings suggest that H2 inhalation may represent a feasible and safe approach to limiting sepsis-induced cognitive deterioration.

Mechanism

H2 inhalation suppresses neuroinflammation in the hippocampus and prefrontal cortex while upregulating total Nrf2 protein, thereby modulating antioxidant and anti-inflammatory gene expression and attenuating sepsis-induced memory deficits.