The iron chelator deferoxamine (DFX) is efficacious in ameliorating hypoxic-ischemic brain injury. However, the effect of DFX worked in the ischemic and the mechanism is still unclear. Recent studies have shown that apoptosis and oncosis may be the pathways of cell death accountable for astrocytic death in the ischemic core. The effect of DFX on primary cultures of rat astrocytes later subjected to modified oxygen and glucose deprivation (OGD), which can mimic the circumstances in the ischemic core, was evaluated in this study. DFX pretreatment significantly suppressed cell death and ameliorated the cellular swelling of astrocytes in the ischemic core, especially after 3 h of OGD. The release of lactate dehydrogenase (LDH) and the production of reactive oxygen species (ROS) were reduced by DFX pretreatment. DFX reduced the expression level of active caspase-3 and increased the expression level of HIF-1 α in astrocytes induced by 3 h of OGD, but had no effect on aquaporin-4 (AQP4) expression. We conclude that DFX suppresses both apoptosis and oncosis in astrocytes in an in vitro model of the ischemic core. [ABSTRACT FROM AUTHOR]