Effect of nimodipine pretreatment on postoperative cognitive function in rats with chronic cerebral ischemia

Abstract

Objective To evaluate the effect of nimodipine pretreatment on postoperative cognitive function in rats with chronic cerebral ischemia. 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: chronic cerebral ischemia operation group(group H) and nimodipine plus chronic cerebral ischemia operation group(group N+ H). The chronic cerebral ischemia model was established by permanently ligating bilateral common carotid arteries of chloral hydrate-anesthetized rats.Rats underwent Morris water maze adaptive training for 5 days 2 weeks later.Nimodipine 1 mg/kg was intraperitoneally injected on 1st day after the end of adaptive training in group N+ H, while the equal volume of normal saline was given instead in group H, and 30 min later splenectomy was performed under sevoflurane anesthesia in two groups.Ten rats in each group were selected on 1 day before operation and 3 and 7 days after operation and underwent Morris water maze test to assess cognitive function.The rats were then sacrificed, brains were removed, and hippocampal tissues were isolated for determination of apoptosis in hippocampal neurons and intracellular Ca2+ concentrations([Ca2+ ]i) in cytoplasm and 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 baseline at 1 day before operation, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the apoptotic rate and [Ca2+ ]i were increased, Bcl-2 mRNA expression was down-regulated, and 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 H, 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, and Bax mRNA expression was down-regulated, and Bax mRNA/Bcl-2 mRNA ratio was decreased at each time point after operation in group N+ H(P<0.05). Conclusion Nimodipine pretreatment can improve the postoperative cognitive function of rats with chronic cerebral ischemia, and the mechanism may be related to inhibiting calcium overload-induced apoptosis in hippocampal neurons. Key words: Nimodipine; Cerebral ischemia; Cognition disorders