Shock/sepsis/trauma/critical careHydrogen sulfide attenuates surgical trauma-induced inflammatory response and cognitive deficits in mice

BackgroundIt has been increasingly reported that peripheral surgical trauma triggers neuroinflammatory processes associated with postoperative cognitive dysfunction, and that mitigating the neuroinflammatory effects of surgery prevents surgery-induced cognitive dysfunction. Endogenously produced hydrogen sulfide (H2S) has multiple functions in the brain, and an increasing number of studies have demonstrated its anti-inflammatory effects. The present study was designed to investigate the effects of sodium hydrosulfide (NaHS), an H2S donor, on the cognitive impairment of mice as they experience neuroinflammatory changes induced by surgery.MethodsEach mouse received 5 mg/kg NaHS or volume-matched vehicle administration by intraperitoneal injection once daily, 3 d before surgery, on the day of surgery, and for 3 d afterward. We assessed cognitive function using a Morris water maze and evaluated expression of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the serum and hippocampus. We performed each test 1, 3, and 7 d after surgery.ResultsHippocampal-dependent memory impairment in mice after surgery was associated with increased serum proinflammatory cytokines, as well as proinflammatory cytokine expression in the hippocampus. Presurgery treatment with NaHS, an H2S donor, significantly attenuated surgery-induced memory impairment and expression of proinflammatory cytokines in the serum and hippocampus.ConclusionsThese findings suggest that intraperitoneal injections of NaHS could significantly mitigate surgery-induced memory impairment in mice, which is strongly associated with reduced levels of serum and hippocampal proinflammatory cytokines.