Long-term effects of dexmedetomidine on the brain development in propofol-induced neonatal rats / 临床麻醉学杂志

ABSTRACT

Objective To explore the long-term effects of dexmedetomidine on the brain development in propofol-induced neonatal rats.Methods Thirty-five seven-day-old Sprague-Dawley rats of both genders,weighing 10-15 g,were randomly divided into seven groups (n =5) using a random number tablenormal saline group (group N),intralipid group (group F),propofol 100 mg/kg group (group P),dexmedetomidine 75 μg/kg (group D),dexmedetomidine 25 μg/kg,50 μg/kg and 75μg/kg+propofol 100 mg/kg groups (groups PD25,PD50 and PD75),neonatal rats in each group were treated according to the corresponding dosing regimen.After fully awake,the rats were allowed to mature until postnatal week 9 and the spatial learning and memory capacities were tested by Morris water maze.The rats were sacrificed after the tests.Brain was sliced for determination of hippocampal apoptosis by TUNEL assays and the expression of postsynaptic density protein 95 (PSD95) by immunohistochemistry.Results Compared with group N,the escape latency was significantly prolonged,the times of platform crossing were significantly decreased,the hippocampal apoptosis ratio was significantly increased and the expression of PSD95 was significantly down-regulated in groups P,PD25 and PD50 (P＜0.05).Compared with group P,the escape latency was significantly shortened,the times of platform crossing were significantly increased and the hippocampal apoptosis were significantly decreased in groups PD50 and PD75 (P＜0.05),the expression of PSD95 was up-regulated in group PD75 (P＜0.05).Compared with group PD25,the escape latency was significantly shortened,the number of platform crossing was significantly increased and the hippocampal apoptosis were significantly decreased in groups PD50 and PD75 (P＜0.05),the expression of PSD95 was significantly up-regulated in group PD75 (P＜0.05).Compared with group PD50,the hippocampal apoptosis were significantly decreased,the expression of PSD95 was significantly up-regulated in group PD75 (P＜ 0.05).Conclusion The addition of dexmedetomidine 50,75 μg/kg attenuates propofol-induced neurocognitive impairment in neonatal rats after aducthood,partially by attenuating hippocampal apoptosis and upregulating the expression of PSD95.Dexmedetomidine alone was not neurotoxic to the developing brain.