Icaritin Promotes Brain Functional Rehabilitation in Ischemic Stroke Rats by Regulating Astrocyte Activation and Polarization Via GPER

Cerebral ischemic injury induces the polarization of astrocytes toward two different phenotypes, i.e., the proinflammatory A1 phenotype and the protective, anti-inflammatory A2 phenotype, affects the prognosis of cerebral ischemia. To explore the neuroprotective effect of phytoestrogens Icaritin (ICT) on cerebral ischemic rehabilitation and the preliminary mechanism of regulating astrocyte polarization. The Transient middle cerebral artery occlusion (tMCAO)/reperfusion was performed on male adultsand then treated with ICT (i.p.) once daily for 28 days. Intervention of G protein-coupled estrogen receptor (GPER) specific inhibitor G15 was repeated. The body weight, Garcia JH scale, right/left brain weight ratio, CatWalk gait test and Y maze test to assess overall neural function in rats. Cytokines in ischemic cortical were detected by ELISA. And the double immunofluorescence staining and Western blotting to evaluated the activation and A1 and A2 polarization of astrocytes. The results showed that ICT treatment markedly perfected functional outcomes on a long-term basis after ischemic stroke, it also improved learning and memory and gait. ICT inhibited the polarization of A1 type astrocytes and promoted the polarization of A2 type astrocytes, promote neuron regeneration in hippocampus dentate gyrus (DG) region. G15 removes some of the protective effects of ICT. The experimental results show that ICT exerts neuroprotective effects and regulates astrocyte polarization through GPER, suggesting that it may be a potential therapeutic agent for ischemic stroke during the recovery period.