Fluoxetine Increases Astrocyte Survival And Inhibits Glial Scar Formation After Cerebral Ischemia And Hypoxia

Aim: To investigate the mechanisms of fluoxetine on astrocyte survival and the formation of glial scar after cerebral ischemia and hypoxia in vitro.Methods: After isolation,purification and culture of SD rat primary cortical astrocytes,the fourth generation of astrocyte were randomly divided into 6 groups,the change of astrocyte cellular morphology were observed at the time of 6h OGD and 24 h reperfusion.Cell viability was assayed with LDH method,At the end of reperfusion,Autophagy-related protein LC3-II,CathepsinD,Beclin-1,p62,p-ULK1,GFAP,Phosphacan levels were determined.Results: Compared with cont group,LDH leakage of astrocyte can be enhanced in OGD,fluoxetine postconditioning reduced LDH leakage after reperfusion(P=0.001)concomitant with decreasing LC3-II(P=0.009),Beclin-1(P=0.009),P62(P=0.007),p-ULK(P=0.008),Cathepsin D(P=0.008),GFAP(P=0.022),Phosphacan(P=0.017);Compared with OGD+flux group,CQ eliminate the protective effect of fluoxetine,concomitant with increase p62(P=0.01),LC3-II(P=0.008),Beclin-1(P=0.009),p-ULK1(P=0.02),Cathepsin D(P=0.007),GFAP(P=0.029),Phosphacan(P=0.0075).Conclusion: Fluoxetine has protective effect on astrocytes which are exposure to cerebral ischemia and hypoxia through autophagy / lysosome pathway and increase autophagy flow in vitro.