Here we demonstrate by using our novel strain of myeloid-specific Hif-ɑ knockout (KO) mice that HIF-1α, but not HIF-2α in microglia critically affects neuronal survival in mice following ischemic stroke by regulating CD36 or milk fat globule-epidermal growth factor 8 (MFG-E8)-mediated phagocytosis, which in turn leads to reactive oxygen species (ROS) and TNF-α production. Here, EPAS1 is linked to ischemic stroke.