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

Objective: This 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. Methods: Healthy 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 30 min later under 1.8% isoflurane inhalation for 2 h. In remaining groups, rats received injection of 1 mg/kg nimodipine (i.p) and/or 4 ml/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. Results: When 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. Conclusion: Pre-treatment with both nimodipine and 7.5% HS exerts better protective effects, which is related to the inhibition of hippocampal neuronal apoptosis. (C) 2016 Elsevier B.V. All rights reserved.