Effect Of Nimodipine Premedication On Postoperative Cognitive Function In Rats With Cerebral Ischemic Stroke

Objective:Postoperative cognitive dysfunction is one of the common complications after surgery,which manifests as memory loss,directional impairment and social ability change.It can lead to increase hospitalization and medical costs,delay in recovery,and affect the quality of life after surgery.Therefore,it is of great significance to prevent its occurrence.To evaluate the effect of premedication with nimodipine on postoperative cognitive function in rats with cerebral ischemic stroke.Methods:One hundred and twenty healthy male Sprague-Dawley rats,aged 3 months,weighing 250-350g,were randomly divided into 4 groups?n=30 each?using a random number table:Normal saline+surgery group?group C?,Nimodipine+surgery group?group N?,Normal saline+cerebral ischemic stroke surgery group?group NS+I?,and Nimodipine+cerebral ische-mic stroke surgery group?group N+I?.The cerebral ischemic stroke model was established by thread occlusion in NS+I and N+I groups.Three weeks later,the rats in N and N+I groups were injected intraperitoneally with 1 mg/kg nimodipine,rats in group C and NS+I were given the same volume of normal saline,30 min late,four groups of rats underwent exploratory laparotomy under1.7%sevoflurane anesthesia.Behavioral tests?Morris water maze?were performed 1 day before surgery and 3 and 7 days after surgery to detect cognitive function in rats.After the end of Morris water maze test,rats were selected and sacrificed,brains were removed,and flow cytometry was used to detect hippocampal neuronal apoptosis rate and cintracellular Ca²⁺concentration([Ca²⁺]_i)in cytoplasm,and Western blot method was used to detect the expression levels of Bcl-2 and Bax in the hippocampus.Results:1.Morris water maze test results:Compared with the value at 1 day before operation,the escape latency was prolonged,the times of crossing the platform was decreased at every time point after operation in NS+I group and N+I group?P<0.05?.Compared with the C group,the escape latency was prolonged,the times of crossing the platform was decreased at every time point in group NS+I?P<0.05?.Compared with the N group,the escape latency was prolonged,the times of crossing the platform was decreased at every time point in group N+I?P<0.05?.Compared with the N+I group,the escape latency was prolonged,the times of crossing the platform was decreased at every time point after operation in NS+I group?P<0.05?.2.The results of apoptosis in hippocampus and intracellular Ca²⁺concentration([Ca²⁺]_i)in cytoplasm:Compared with the value at 1 day before operation,the hippocampal neuronal apoptosis rate and intracellular Ca²⁺concentration([Ca²⁺]_i)in cytoplasm were increased at each time point after operation in NS+I group and N+I group?P<0.05?.Compared with the C group,the hippocampal neuronal apoptosis rate and intracellular Ca²⁺concentration([Ca²⁺]_i)in cytoplasm were increased at each time point in group NS+I?P<0.05?.Compared with the N group,the hippocampal neuronal apoptosis rate and intracellular Ca²⁺concentration([Ca²⁺]_i)in cytoplasm were increased at each time point in group N+I?P<0.05?.Compared with the N+I group,the hippocampal neuronal apoptosis rate and intracellular Ca²⁺concentration([Ca²⁺]_i)in cytoplasm were increased at each time point after operation in NS+I group?P<0.05?.3.The results of Western blot:Compared with the value at 1 day before operation,the expression levels of Bcl-2 was down-regulated,the expression levels of Bax was up-regulated at every time point after operation in NS+I group and N+I group?P<0.05?.Compared with the C group,the expression levels of Bcl-2 was down-regulated,the expression levels of Bax was up-regulated at every time point in group NS+I?P<0.05?.Compared with the N group,the expression levels of Bcl-2 was down-regulated,the expression levels of Bax expression was up-regulated at every time point in group N+I?P<0.05?.Compared with the N+I group,the expression levels of Bcl-2 was down-regulated,the expression levels of Bax was up-regulated at every time point after operation in NS+I group?P<0.05?.Conclusion:Nimodipine premedication can improve the postoperative cognitive function of rats with cerebral ischemic stroke.The mechanism may be related to the inhibition of hippocampal neuronal apoptosis induced by calcium overload.