Abstract： [Objective]To investigate the cytotoxic effect ofaquaporin-4 (AQP4) antibody onin vitro cultured rat cortical neurons.[Methods]Cortical cells were obtained from Wistar embryonic rats with 16-19-d pregnancy;3 daRer seeding,the cultured cortical cells were randomly divided into a control group and an AQP4 antibody-positive serum treatment group.Neurons of the control group were added the normal human serum and those in the treatment group were added serum from AQP4 antibody positive patients.The number and morphology changes of astrocytes,neurons and microglias were observed by immunohistochemistry at 2,4 and 6 h after being incubated with AQP4 antibody positive serum or controls.[Results] No number or morphology changes of cortical cells were observed in control group at different time points.AQP4 antibody-positive serums induced astrocyte swelling,microglia hyperplasia and neuron axonotmesis,but did not influence the numbers of cortical cells at 2 h after induction.The numbers of astrocytes and neurons in the treatment group (24.73％±5.27％ and 35.49％±8.43％,respectively) significantly decreased as compared with those in the control group (30.34％％:t,4.53％ and 48.60％+10.99％) at 4 h after induction (P＜0.05),while those of microglias in the treatment group (27.35％±13.17％) obviously increased as compared with those in the control group (16.44％±2.70％,P＜ 0.05);these changes became more significant at 6 h after induction.[Conclusion] AQP4 antibodies induce loss of astrocytes and neurons,and microglia activation in primary cortical cells,which maybe imply the primary pathogenic role of AQP4 antibody in neuromyelitis optica.