Effects Of Different Duration Of Sevoflurane Anesthesia In Neonatal Period On Long-term Cognitive Function In Rats

Backgroud:Over the past twenty years with the rapid progress of anesthesia and surgery technology,general anesthesia has been widely used in fetal,neonatal,infant,even premature.But with the increase in the number of anesthesia,postoperative neurological complications such as cognitive dysfunction also showed an increasing trend,except for eidly patients,pediatric patients also exist postoperative cognitive dysfunction.Therefore,for the safety of children the anesthesiologist,neurologists,parents and media focus the attention to the effect of general anesthesia on learning and memory function.Their main concern is whether or not general anesthetics will damage fetal and neonatal,infant and children’s long-term cognitive function.Sevoflurane is the most common volatile anesthetic in pediatric anesthesia because of its low blood/gas partition coefficient,rapid onset and offset.Previous studies showed that sevoflurane could induce neuron apoptosis and neurodegeneration,further study found that synaptic plasticity change that sevoflurane induced may be the cellular basis of learning and memory changes because of the close relationship between hippocampal synaptic plasticity and cognitive function.However,the conclusions about the effect of deferent-duration sevoflurane anesthesia on neonatal rats cognitive function are not clear.The present study was designed to investigate the effects of sevoflurane anesthesia on long-term cognitive function and synaptic plasticity in hippocampus of neonatal rats.Part One The effect of different duration sevoflurane anesthesia in neonatal period on hippocampal neurons apoptosis in ratsObjective:To observe the effect of different duration sevoflurane anesthesia in neonatal period on hippocampal neurons apoptosis in rats.Methods:Healthy SD neonatal rats aged 7 days were enrolled.They were randomly divided into three groups:C,S1 and S2 group.The group S1 and S2 inhaled 2%sevoflurane and 30%oxygen for 2 and 6 h,the rat pups in the control group received no treatment.At 6 h after sevoflurane anesthesia the rat pups were killed through taking off the neck,then 4%paraformaldehyde was perfusion and the brain slices were made for Tunel staining.Results:Compared with group C,the neuron apoptosis was more than group S1 and group S2(P<0.05);Compared with the group Si,the neuron apoptosis was greater in group S2(P<0.05).Conclusion:Sevoflurane anesthesia may result in neoron apoptosis in the developing rat brain,and the apoptosis show time-dependent.Part Two The effects of different duration of sevoflurane anesthesia in neonatal period on long-term cognitive function in ratsObjective:To observe the effects of different duration of sevoflurane anesthesia in neonatal period on long-term cognitive function in rats.Methods:Healthy SD neonatal rats aged 7 days were enrolled.They were randomly divided into three groups:C,S1 and S2 group.The group S1 and S2 inhaled 2%sevoflurane and 30%oxygen for 2 and 6 h,the rat pups in the control group received no treatment.Long-term cognitive function were tested by the Morris water maze at 30 d after sevoflurane exposure(postnatal 37 d).Results:Compared with group C,the escape latency at 4,5 d in group S1 and at 2-5 d in group S2 significantly longer during Morris water maze test training period(P<0.05);the platform crossing times significantly reduced and the time spent in the platform quadrant was significantly longer in the group Si and group S2 during Morris water maze test exploration period(P<0.05);Compared with the group S1,the platform crossing times were not significantly different(P>0.05);the time spent in the platform quadrant in the group S2 was significantly longer(P<0.05).Conclusion:Sevoflurane anesthesia in neonatal period can result in long-term learning and memory dysfunction in rats,the insult shows time-dependent.Part Three The effects of different duration sevoflurane anesthesia in neonatal period on hippocampus synaptic plasticity in ratsObjective:To observe the effects of different duration sevoflurane anesthesia in neonatal period on hippocampus in rats.Methods:Healthy SD neonatal rats aged 7 days were enrolled.They were randomly divided into three groups:C,S1 and S2 group.The group S1 and S2 inhaled 2%sevoflurane and 30%oxygen for 2 and 6 h,the rat pups in the control group received no treatment.Long-term cognitive function were tested by the Morris water maze at 30 d after sevoflurane exposure(postnatal 37 d).After the water maze behavioral test,rats were euthanatized,hippocampus tissues were harvested and expressions of BDNF,PSD-95 and Synapsin-1 in hippocampus tissues were detected by western blotting.Results:Compared with group C,the expression of BDNF、PSD-95 and Synapsin-I in hippocampus tissues of in group S2 remarkably decreased(P<0.05).Compared with the group S1,the expression of BDNF、PSD-95 and Synapsin-I in hippocampus tissues in the group S2 remarkably decreased(P<0.05).Conclusion:Sevoflurane anesthesia in neonatal period can result in long-term cognitive dysfunction in rats,the mechanism was partly associated with the impairment of hippocampus synaptic plasticty.