The Long-Term Effects Of Propofol On Brains Of Neonatal Rats

Objective:To observe the long-term effects of propofol on brains of neonatal rats and to explore the possible mechanisms.Methods:175Sprague Dawley rats aged7d were randomly divided into5groups (n=35each). The rats in propofol groups were intraperitoneally injected with25mg/kg (P1group),50mg/kg (P2group),100mg/kg (P3group) or200mg/kg (P4group) propofol respectively, while the rats in control group (P0group) were injected with no drugs. The rats were risen up until9-week-old. Breathing and metabolic indexes were detected by blood gas analyzer. The rats were tested for spatial learning and memory in Morris water maze (MWM). The ultrastructure of hippocampal neurons was observed by transmission electron microscope. The expression of NeuN and caspase-9in hippocampus was observed by immunohistochemistry method. The expression of NGF and caspase-9in hippocampus was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot techniques.Results:Breathing and metabolic indexes were not different among five groups. Compared with P0group, the escape latency was longer and the frequency of passing through the platform was decreased in P2group, P3group and P4group. The structure of hippocampal neurons and synapsis was normal in PO group and P1group, while50mg/kg or100mg/kg propofol resulted in nuclear blebbing, chromatin andsynaptic versicle decreasing,200mg/kg propofol led to nuclear fragmentation, chromatin condensation and apoptotic bodies, and the structure of the synaptic was injured. Compared with P0group, NeuN-positive stained neurons were deceased while caspase-9-positive neurons were increased in CA1, CA3and dentate gyrus regions of hippocampus in P1group, P2group, P3group and P4group. Moreover, compared with P0group, NGF mRNA and protein were downregulated while caspase-9mRNA and protein were upregulated in P1group, P2group, P3group and P4group.Conclusion:Propofol may have long-term effects on brains and impair spatial learning and memory in neonatal rats by downregulating NeuN and NGF, upregulating caspase-9and inducing apoptosis of hippocampal neurons.