Effect of dexmedetomidine on ketamine anesthesia-induced apoptosis in hippocampal neurons of juvenile rats

Abstract

Objective To investigate the effect of dexmedetomidine on ketamine anesthesia-induced apoptosis in hippocampal neurons of juvenile rats. Methods Seventy-five pathogen-free Sprague-Dawley rats of both sexes, aged 7 days, weighing 11-16 g, were randomly divided into 5 groups(n=15 each)using a random number table: control group(group C), ketamine anesthesia group(group K)and dexmedetomidine 1, 4 and 8 μg/kg groups(Dex1, Dex2 and Dex3 groups). Normal saline 0.1 ml was intraperitoneally injected in group C. Ketamine 50 mg/kg was intraperitoneally injected in group K. A mixture(0.1 ml)of ketamine 50 mg/kg and dexmedetomidine 1, 4 and 8 μg/kg was intraperitoneally injected in Dex1, Dex2 and Dex3 groups, respectively.After righting reflex recovered completely, the rats were put back into the cage, and 1 h later 5 rats in each group were sacrificed.Hippocampi were removed for determination of the expression of phosphor-Akt(p-Akt), Akt, activated caspase-3, caspase-3, Bax, Bcl-2 and post-synaptic density protein 95(PSD-95)by Western blot.The ratio of p-Akt/Akt and activated caspase-3/caspase-3 were calculated.Ten rats in each group were selected on postnatal day 30 and underwent Morris water maze test 3 times a day for 5 consecutive days. Results Compared with group C, the escape latency was significantly prolonged on 3rd-5th days, the exploration time was shortened, p-Akt/Akt ratio was decreased, activated caspase-3/caspase-3 ratio was increased, the expression of PSD-95 and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group K. Compared with group K, the escape latency was significantly shortened on 3rd-5th days, the exploration time was prolonged, p-Akt/Akt ratio was increased, activated caspase-3/caspase-3 ratio was decreased, the expression of PSD-95 and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in Dex1, Dex2 and Dex3 groups.The escape latency was significantly shorter on 4th-5th days, and the exploration time was longer in Dex2 and Dex3 groups than in Dex1 group.There was no significant difference in p-Akt/Akt ratio, activated caspase-3/caspase-3 ratio, and expression of PSD-95, Bax and Bcl-2 between Dex1, Dex2 and Dex3 groups. Conclusion Dexmedetomidine reduces ketamine-induced apoptosis in hippocampal neurons through activating hippocampal Akt and up-regulating PSD-95 expression in juvenile rats. Key words: Dexmedetomidine; Ketamine; Cognition disorders; Apoptosis; Hippocampus; Neurons; Child