Our previous investigation showed that TOPK attenuate the oxidative stress during the acute stage following stroke through activating Akt pathway, and the present results indicate that TOPK may ameliorate brain ischemia-reperfusion injury during the recovery stage by driving a shift of microglia/ macrophages towards the M2 phenotype through the phosphorylation of HDAC1 and HDAC2, suggesting TOPK functions through different mechanism at different stage following stroke, which could become a promising target for new drug development in the treatment of ischemic stroke. The gene discussed is AKT1; the disease is ischemic stroke.