Ropivacaine anesthesia during pregnancy affects the emotion and learning and memory ability of SD model offspring through NGF/ERK/CREB pathway
Objective To investigate the effect of ropivacaine anesthesia during pregnancy on offspring's emotion and learning and memory ability and its potential mechanism.Methods A pregnant rat model was established to investigate the neurocognitive effects of ropivacaine anesthesia on offspring during the second trimester.The behavior was tested on the first few days after birth(P25-30)(Morris water maze and conditioned fear test).In addition,the hippocampal morphology(P30)of the offspring was detected by Nissl staining,and the density of hippocampal dendritic spines was determined by Golgi staining.Hippocampal nerve growth factor(NGF),extracellular signal-regulated kinase(ERK)and phosphorylated-ERK(p-ERK)were determined by Western blotting.The protein levels of yclic adenosine monophosphate response element-binding(CREB),p-CREB,synaptophysin(SYP),synapsin(SYN)and postsynaptic density-95(PSD95).In addition,SCH772984(an ERK inhibitor)was used to evaluate the role and potential mechanism of the ERK pathway in PC 12 cells.Results The results showed that ropivacaine anesthesia could lead to long-term neurocognitive dysfunction,reduce the density of dendritic rota-tion,lead to neuronal loss,and down-regulate the expression of NGF,ERK,p-ERK,mitogen and stress-activated protein kinase(MSK),CREB,p-CREB,SYP,SYN and PSD95 in hippocampus.Conclusion Ropivacaine-induced maternal anesthesia during fetal brain development can lead to long-term neurocognitive dysfunction in offspring,which may occur by inhibiting the NGF/ERK/CREB pathway in the hippocampus.