Pre-treatment with nimodipine and 7.5% hypertonic saline protects aged rats against postoperative cognitive dysfunction via inhibiting hippocampal neuronal apoptosis

Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Zhang Qi, Yuan Tianbao, Li Yanan, Xin Xi, He Jinhua, Wang Qiujun
ObjectiveThis study aimed to investigate the effects of pre-treatment with nimodipine and 7.5% hypertonic saline (HS) on postoperative cognitive dysfunction (POCD) in aged rats.MethodsHealthy Sprague-Dawley aged rats were randomly assigned into 4 groups: POCD group, nimodipine group, HS group, and nimodipine+HS group. Rats in POCD group received normal saline injection and then splenectomy 30min later under 1.8% isoflurane inhalation for 2h. In remaining groups, rats received injection of 1mg/kg nimodipine (i.p) and/or 4ml/kg 7.5% HS (i.v) and then splenectomy. Morris water maze test was performed before and after surgery. The hippocampus was harvested for the detection of neuronal apoptosis rate (AR), cytoplasmic calcium ([Ca²⁺]i), Bcl-2 and Bax mRNA expression and hippocampal neuronal ultrastructure.ResultsWhen compared with POCD group, the latency to escape, neuronal AR, [Ca²⁺]i, Bax mRNA expression and Bax/Bcl-2 ratio reduced dramatically, but the times of crossing the platform and Bcl-2 mRNA expression increased significantly (P<0.05) in nimodipine group, NS group and nimodipine+HS group. In addition, the latency to escape, neuronal AR, [Ca²⁺]i, Bax mRNA expression and Bax/Bcl-2 ratio reduced markedly, but the times of crossing the platform and Bcl-2 mRNA expression increased significantly in nimodipine+HS group as compared to nimodipine group and NS group (P<0.05). Hippocampal neuronal ultrastructure damage was observed in all 4 groups, but it was the mildest in nimodipine+HS group.ConclusionPre-treatment with both nimodipine and 7.5% HS exerts better protective effects, which is related to the inhibition of hippocampal neuronal apoptosis.



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