Effects of propofol anesthesia on long-term cognitive function in neonatal rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of different doses of propofol anesthesia on the long-term cognitive function in neonatal rats.Methods One hundred 7-day-old male Sprague-Dawley rats,weighing 9-18 g,were randomly divided into 5 groups (n =20 each) ∶ control group (C group) and propofol 25,50,100 and 200mg/kg groups (groups P1-4,respectively).Groups P1 and P2 received intraperitoneal propofol 25 and 50 mg/kg,respectively.Groups P3 and P4 received intraperitoneal propofol 100 and 200 mg/kg,respectively,and after righting reflex completely recovered,an increment of propofol 50 mg/kg was given until the total amount was finished.Five animals in each were chosen and arterial blood samples were obtained immediately after the animals were fully awake for blood gas analysis.The rats were then continuously fed.When the rats were 9 weeks old,the spatial learning and memory function was tested by Morris water maze.The animals were then sacrificed and their brains were removed for detection of the expression of nerve growth factor (NGF) and Caspase-9 protein and mRNA in hippocampal tissues (by Western blot analysis and RT-PCR) and for microscopic examination of the ultrastructure of hippocampal neurons.Results There was no significant difference in blood gas analysis index between the 5 groups (P ＞ 0.05).Compared with group C,no significant change was found in the escape latency and frequency of crossing the original platform in group P1,the escape latency was prolonged and the frequency of crossing the original platform was decreased in groups P2-4,the expression of NGF protein and mRNA was down-regulated and the expression of Caspase-9 protein and mRNA was up-regulated in groups P1-4 (P ＜ 0.05).The escape latency was gradually prolonged,the expression of NGF protein and mRNA was gradually down-regulated and the expression of Caspase-9 protein and mRNA was gradually up-regulated in groups P1-4.The frequency of crossing the original platform was decreased in groups P2-4 compared with group P1 (P ＜ 0.05).There was no significant difference in the frequency of crossing the original platform between groups P2-4 (P ＞ 0.05).Nucleus condensation,chromatin condensation,nuclear fragmentation and apoptotic bodies were observed in groups P2-4.Conclusion Propofol anesthesia can impair the long-term cognitive function in neonatal rats,the effect is related to the dose,and inhibition of NGF expression and increase in the activity of Caspase-9 may be involved in the mechanism.