Pretreatment with nimodipine reduces incidence of POCD by decreasing calcineurin mediated hippocampal neuroapoptosis in aged rats

Abstract

Background: Calcineurin (CaN) having a high expression in hippocampal neurons is closely related to apoptosis. Pretreatment with nimodipine can lower the apoptosis rate of hippocampal neuron to reduce the incidence of postoperative cognitive dysfunction (POCD). However, the relationship between cerebral protective effect of pretreatment with nimodipine and CaN is controversial in the literature. The aim of this study is to evaluate the relationship between neuroprotective effect of nimodipine and CaN on POCD in aged rats. Methods: Ninety-six 18-month-old male Sprague-Dawley rats were randomly assigned into 4 groups (n=24 each): control group (Group C), nimodipine group (Group N), surgery group (Group S) and nimodipine + surgery group (Group N+S). In Group N and Group N+S, nimodipine 1 mg/kg was intraperitoneally injected, while the equal volume of normal saline was given instead in Group S. 30 min later, Group N and Group C inhaled pure oxygen for 2 h, and Group S and N+S inhaled 3% sevoflurane for 2 h when exploratory laparotomy was performed. Morris water maze test was performed on 1 day before operation and 1, 3 and 7 days after operation. After the end of Morris water maze test at 1 day before operation and 1 and 7 days after operation, 8 rats were sacrificed, brains were removed and hippocampal tissues were obtained for detection of apoptosis in hippocampal neurons, cytoplasmic calcium ([Ca 2+ ] i ), and hippocampal CaN and caspase-3 expression. Results: Compared with the 1st day before operation, the escape latency, apoptosis rate, [Ca 2+ ] i , expression of CaN and caspase-3 increased significantly, but the frequency of crossing the original platform decreased dramatically in Group S and N+S(P<0.05). In addition, the escape latency, apoptosis rate, [Ca 2+ ] i , and expression of CaN and caspase-3 decreased markedly, but the frequency of crossing the original platform increased significantly in Group N+S as compared with Group S (P<0.05). Conclusions: Pretreatment with nimodipine reduces the incidence of POCD by decreasing CaN mediated hippocampal neuroapoptosis in aged rats.