Effect of nimodipine pretreatment on postoperative cognitive function in rats with cerebral ischemic stroke / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of nimodipine pretreatment on postoperative cognitive function in rats with cerebral ischemic stroke.Methods Sixty healthy male Sprague-Dawley rats,aged 3 months,weighing 250-350 g,were divided into 2 groups (n =30 each) using a random number table method:normal saline plus cerebral ischemic stroke group (group Ⅰ) and nimodipine plus cerebral ischemic stroke group (group N+Ⅰ).The cerebral ischemic stroke model was established by thread occlusion in two groups.Three weeks later,nimodipine 1 mg/kg was intraperitoneally injected in group N+Ⅰ,while the equal volume of normal saline was given instead in group Ⅰ,and 30 min later two groups underwent exploratory laparotomy under 1.7％ sevoflurane anesthesia.Eight rats in each group were randomly selected on 1 day before operation and 3 and 7 days after operation,and Morris water maze test was performed to assess cognitive function.The rats were then sacrificed,brains were removed,and hippocampal tissues were isolated for detection of apoptosis in hippocampal neurons,intracellular Ca2+concentration ([Ca2+]i) in cytoplasm and the expression of Bcl-2 and Bax mRNA (by real-time polymerase chain reaction).The ratio of Bax mRNA to Bcl-2 mRNA was calculated.Results Compared with the value at 1 day before operation,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,apoptotic rate and [Ca2+] i were increased,Bcl-2 mRNA expression was down-regulated,Bax mRNA expression was up-regulated,and Bax mRNA/Bcl-2 mRNA ratio was increased at each time point after operation in two groups (P＜0.05).Compared with group Ⅰ,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the apoptotic rate and [Ca2 +]i were decreased,Bcl-2 mRNA expression was up-regulated,Bax mRNA expression was down-regulated,and Bax mRNA/Bcl-2 mRNA ratio was decreased at each time point after operation in group N+Ⅰ (P＜0.05).Conclusion Nimodipine pretreatment can improve the postoperative cognitive function of rats with cerebral ischemic stroke,and the mechanism may be related to inhibiting calcium overload-induced apoptosis in hippocampal neurons.