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Due to the potential tumorigenicity and low survival rate of transplanted cells, focuses have been shifted from cell replacement to their paracrine effects. Therefore, stem cell\u2010conditioned medium (CM) therapy has emerged as an alternative candidate. Here, we investigated the effect of CM derived from human embryonic MSCs on experimental ischemic stroke. Wistar rats underwent ischemic stroke by the right middle cerebral artery occlusion (MCAO). CM was infused either one time (1\u2009hr post\u2010MCAO) or three times (1, 24, and 48\u2009hr post\u2010MCAO) through guide cannula into the left lateral ventricle. Neurological functions were evaluated using Bederson's test and modified Neurological Severity Score on Days 1, 3, and 7 following MCAO. Infarction volumes and cerebral edema were measured on Days 3 and 7. growth\u2010associated protein\u201043, synaptophysin, cAMP response element\u2010binding protein, and phosphorylated\u2010cAMP response element\u2010binding protein levels were also assessed in peri\u2010ischemic cortical tissue on Day 7 postsurgery. Our results indicated that three times injections of CM could significantly reduce body weight loss, mortality rate, infarct volumes, cerebral edema, and improve neurological deficits in MCAO rats. Moreover, three injections of CM could restore decreased levels of synaptic markers in MCAO rats up to its normal levels observed in the sham group. Our data suggest that using the CM obtained from embryonic stem cells\u2013MSCs could be a potent therapeutic approach to attenuate cerebral ischemia insults which may be partly mediated through modulation of synaptic plasticity.<\/jats:p>","DOI":"10.1002\/jcp.29981","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T23:58:04Z","timestamp":1596153484000},"page":"1967-1979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["The conditioned medium of human embryonic stem cell\u2010derived mesenchymal stem cells alleviates neurological deficits and improves synaptic recovery in experimental stroke"],"prefix":"10.1002","volume":"236","author":[{"given":"Afsaneh","family":"Asgari Taei","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine Tehran University of Medical Sciences  Tehran 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