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Adult male mice (n\u2009=\u2009184) underwent transient middle cerebral artery occlusion, and EPCs were transplanted into the brain immediately after ischemia. Microglial\/macrophage activity and complement receptor 3 (CR3) expression were evaluated in ischemic brains and cultured microglia. CR3 agonist leukadherin-1 was administrated into mice immediately after ischemia to imitate the effects of EPCs. Synaptophysin and postsynaptic density protein 95 (PSD-95) expressions were detected in EPC- and leukadherin-1 treated mice. We found that EPC transplantation increased the number of M2 microglia\/macrophage-phagocytizing apoptotic cells and CR3 expression in ischemic brains at 3 days after ischemia ( p\u2009&lt;\u20090.05). EPC-conditional medium or cultured EPCs increased microglial migration and phagocytosis and upregulated CR3 expression in cultured microglia under oxygen-glucose deprivation condition ( p\u2009&lt;\u20090.05). Leukadherin-1 reduced brain atrophy volume and neurological deficits at 14 days after ischemia ( p\u2009&lt;\u20090.05). Both EPC transplantation and leukadherin-1 increased synaptophysin and PSD-95 expression at 14 days after ischemia ( p\u2009&lt;\u20090.05). EPC transplantation promoted CR3-mediated microglial\/macrophage phagocytosis and subsequently attenuated synaptic loss. Our study provided a novel therapeutic mechanism for EPCs.<\/jats:p>","DOI":"10.1177\/0271678x221135841","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T03:04:23Z","timestamp":1669950263000},"page":"379-392","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Endothelial progenitor cell transplantation attenuates synaptic loss associated with enhancing complement receptor 3-dependent microglial\/macrophage phagocytosis in ischemic mice"],"prefix":"10.1177","volume":"43","author":[{"given":"Yuanyuan","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"Department of Neurology, Ruijin Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 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