The gender difference in effect of sevoflurane exposure on cognitive function and hippocampus neuronal apoptosis in rats

H. Xie, G.-M. She, C. Wang, L.-Y. Zhang, C.-F. Liu

Department of Anesthesiology, The Second Affiliate Hospital of Soochow University, Suzhou, China. chenwangcn@yeah.net

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• Anesthesiology

OBJECTIVE: Anesthesia and surgery can induce postoperative cognitive dysfunction. Ser-133 phosphorylation sites of cAMP-response element binding protein (CREB) is a key gene that mediate a variety of downstream transcription initiation factors, regulate neuronal survival and promote the expression of a large number of genes. Thus, CREB may play a role in this impairment. We hypothesize that and sevoflurane-induced cognitive impairment possibly via inhibiting the expression of CREB downstream genes and proteins.

MATERIALS AND METHODS: To test this hypothesis, adult Sprague-Dawley rats were subjected to sevoflurane exposure and were tested with a series of behavioral experiments (open field, passive avoidance test and Morris water maze test) at different time (1 d to 95 d). Besides, blood gas changes and expiratory sevoflurane concentrations were examined at 2 h; the levels of phosphorylated CREB 1, the protein Bcl-2, Caspase-8 and Caspase-3 were assessed at 1 week and 3 months after anesthesia. We also conducted a comparison in sevoflurane-induced cognitive impairment between male and female rats.

RESULTS AND CONCLUSIONS: Here, we found that sevoflurane anesthesia can impair short-term cognitive function, which may be via down-regulating p-CREB1 and Bcl-2 expression and up-regulating Caspase-8 expression to reduce hippocampus neuronal apoptosis, and male rats suffered a more severe cognitive dysfunction than female rats. In addition, sevoflurane can produce a reversible long-term cognitive dysfunction in rats.

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