Effect of preoperative sleep deprivation on hippocampal TLR4/NF-κB signaling pathway in aged mice with postoperative cognitive dysfunction / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of preoperative sleep deprivation on hippocampal Tolllike receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway in aged mice with postoperative cognitive dysfunction.Methods Sixty clean-grade healthy male C57BL/6J mice,aged 16 months,weighing 28-36 g,were divided into 4 groups (n=15 each) using a random number table method:control group (group C),surgery group (group S),sleep deprivation group (group SD) and sleep deprivation plus surgery group (group SD+S).Mice were fed a common diet in group C.Mice were sleep-deprived for 24 h in group SD.Tibial fracture internal fixation was performed in group S.Tibial fracture internal fixation was performed after 24-h sleep deprivation in group SD+S.Cognitive function was assessed using the contextual fear conditioning test at days 3 and 7 after operation.The animals were sacrificed at day 7 after operation,brains were removed and hippocampi were isolated for determination of tumor necrosis factor-alpha (TNF-α) content (by enzyme-linked immunosorbent assay) and expression of TLR4 and p-NF-κB p65 (by Western blot).Results Compared with group C,the percentage of time spent freezing induced by condition and percentage of time spent freezing induced by context were significantly decreased at days 3 and 7 after operation,the content of TNF-α was increased,and the expression of TLR4 and p-NF-κB p65 was up-regulated in S,SD and SD+S groups (P＜0.05).Compared with group S and group SD,the percentage of time spent freezing induced by condition and percentage of time spent freezing induced by context were significantly decreased at days 3 and 7 after operation,the content of TNF-α was increased,and the expression of TLR4 and p-NF-κB p65 was up-regulated in group SD+S (P＜0.05).Conclusion Preoperative sleep deprivation further accentuates postoperative cognitive dysfunction,and the mechanism is related to activating TLR4/NF-κB signaling pathway and inducing inflammatory responses of aged mice.