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

The central nervous system (CNS) is one of the first physiological systems to be affected in sepsis. During the exacerbated systemic inflammatory response at the early stage of sepsis, circulatory inflammatory mediators are able to reach the CNS leading to neuroinflammation and, consequently, long-term impairment in learning and memory formation is observed. The acute treatment with molecular hydrogen (H-2) exerts important antioxidative, antiapoptotic, and anti-inflammatory effects in sepsis, but little is known about the mechanism itself and the efficacy of chronic H-2 inhalation in sepsis treatment. Thus, we tested two hypotheses. We first hypothesized that chronic H-2 inhalation is also an effective therapy to treat memory impairment induced by sepsis. The second hypothesis is that H-2 treatment decreases sepsis-induced neuroinflammation in the hippocampus and prefrontal cortex, important areas related to short and long-term memory processing. Our results indicate that (1) chronic exposure of hydrogen gas is a simple, safe and promising therapeutic strategy to prevent memory loss in patients with sepsis and (2) acute H-2 inhalation decreases neuroinflammation in memory-related areas and increases total nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates a vast group of antioxidant and inflammatory agents expression in these areas of septic animals.