Abstract The expression of hypoxia-inducible factor-1-alpha (HIF-1α) is up-regulated in ischemic stroke, but its function is still unclear. In the present study, biphasic expression of HIF-1α was observed during 1 to 12 h and after 48 h in neurons exposed to ischemic stress in vitro and in vivo. Treating neurons with 2-methoxyestradiol (2ME2) 0.5 h after ischemic stress or pre-silencing HIF-1α with siRNA decreased brain injury, brain edema, number of apoptotic cell and down-regulate Nix expression. Conversely, apply 2ME2 to neurons 8 h after ischemic stress or silencing the HIF-1α with siRNA 12 h after OGD increased neuron damage and decreased vascular endothelial growth factor (VEGF) expression. Taken together, these results demonstrate HIF-1α induced by ischemia in early and late time leads cellular apoptosis and survival respectively, and provides a new insight into the divergent roles of HIF-1α expression in neurons after ischemic stroke.
