Investigating the effect of preoperative sleep disturbance on perioperative neurocognitive disorders in mice

Abstract

Perioperative neurocognitive disorders (PND) are observed among patients after surgical operations, especially in the elderly, with a spectrum of neuro-disorders including post-operative delirium (POD) and post-operative cognitive dysfunctions (POCD). Meanwhile, sleep disturbance (SD) is commonly experienced among hospitalized patients. Clinical research suggested that preoperative SD is associated with postoperative delirium. We hypothesized that preoperative SD exacerbates neuroinflammation and surgery-induced cognitive dysfunction. On the other hand, general anesthesia has been demonstrated to make a difference in the expression of circadian genes. EGR1 has been proved promoting the transcription of other circadian genes in different tissues including the brain. Therefore, we hypothesized that sevoflurane anesthesia affects EGR1 expression in the brain. Firstly, 24-hour and 72-hour SD was accomplished by mechanical disruption in mice followed by sevoflurane general anesthesia and laparotomy. Neuroinflammatory cytokines and cognitive functions were examined at different time points to determine if preoperative SD exacerbates postoperative neuroinflammation and cognitive dysfunction. Secondly, mice were treated with 2-hour sevoflurane anesthesia. The transcriptional and translational expression of EGR1 was assessed. The results show that neuroinflammation is induced after laparotomy, and preoperative SD is associated with neuroinflammation and cognitive dysfunctions to some extent, but no evidence showing that preoperative SD exacerbates surgery-induced neuroinflammation and cognitive impairment. Sevoflurane general anesthesia induces EGR1 expression in the brain within 4 hours. These studies provide preliminary evidence to better understand the effect of preoperative SD on PND and the role of EGR1 in general anesthesia regulating the circadian rhythm.