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BACKGROUND: Mechanisms underlying general anesthesia-induced neurotoxicity are unclear.Astrocytes have been recognized as important contributors to neuronal development.Until now the response of the astrocytes to neonatal general anesthetics exposure remains unreported.METHODS: Rats of postnatal 7(P7)received 2.5%sevoflurane for 6 h.Expressions of glial fibrillary acidic protein(GFAP)and glutamate-aspartate transporter(GLAST)and phosphorylation of the janus kinase/signal transducer and activator of transcription(JAK/STAT)pathway were detected on day 1,3,7,and 14 after sevoflurane inhalation.In addition,cultured astrocytes were exposed to 2.5%sevoflurane for 2 h and GFAP,GLAST expressions and JAK/STAT phosphorylation were evaluated.Furthermore,we pharmacologically disrupted JAK/STAT signaling in in vivo by treatment with the JAK/STAT inhibitor AG490 and in vitro by treatment with JAK Inhibitor I to detect the consequent expression of GFAP and GLAST.RESULTS: Sevoflurane induced a robust decrease of GFAP and GLAST expression in hippocampal tissue compared with sham control groups at 1-14 d after sevoflurane exposure.Immunohistochemistry showed colocalization of GFAP,GLAST and pSTAT3 in hippocampal CA1 region.Western blot analysis also revealed a significant decrease of pJAK1,pJAK2,and pSTAT3 in the sevoflurane group.In vitro study showed that GFAP,GLAST,pJAK1,pJAK2,and pSTAT3 expressions in cultured astrocytes were remarkably decreased at 24-48 h following sevoflurane treatment.Either AG490 or JAK Inhibitor I significantly decreased expressions of GFAP and GLAST in hippocampus or cultured astrocytes.CONCLUSIONS: Astrocytic GLAST was inhibited by sevoflurane in hippocampus of neonatal rats.Inactivation of JAK/STAT pathway possibly contributes to this effect of sevoflurane.Astrocytic dysfunction induced by sevoflurane may contribute to its neurotoxicity in the developing brain.