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Transplantation of neural stem cells (NSCs) is reported to improve functional outcomes in the animal models of brain ischemia. However, the use of cell therapy is accompanied by adverse effects, so research is growing to use cell\u2010free extracts such as extracellular vesicles (EVs) for targeting brain diseases. In the current study, male Wistar albino rats (20\u2009months old) were subjected to middle cerebral artery occlusion (MCAO). Then, EVs (30\u2009\u03bcg) were injected at 2\u2009hours after stroke onset via an intracerebroventricular (ICV) route. Measurements were done at day 7 post\u2010MCAO. EVs administration reduced lesion volume and steadily improved spontaneous locomotor activity. EVs administration also reduced microgliosis (ionized calcium\u2010binding adaptor molecule 1 (Iba1)<jats:sup>+<\/jats:sup> cells) and apoptotic (terminal\u2010deoxynucleotidyl transferase mediated nick end labelling [TUNEL]) positive cells and increased neuronal survival (neuronal nuclear (NeuN)<jats:sup>+<\/jats:sup> cells) in the ischemic boundary zone (IBZ). However, it had no effect on neurogenesis within the sub\u2010ventricular zone (SVZ) but decreased cellular migration toward the IBZ (doublecortin (DCX)<jats:sup>+<\/jats:sup> cells). The results of this study showed neuroprotective and restorative mechanisms of NSC\u2010EVs administration, which may offer new avenues for therapeutic intervention of brain ischemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance of the study<\/jats:title><jats:p>Based on our results, EVs administration can effectively reduce microglial density and neuronal apoptosis, thereby steadily improves functional recovery after MCAO. These findings provide the beneficial effect of NSC\u2010EVs as a new biological treatment for stroke.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbf.3484","type":"journal-article","created":{"date-parts":[[2019,12,29]],"date-time":"2019-12-29T23:41:22Z","timestamp":1577662882000},"page":"373-383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Effects of neural stem cell\u2010derived extracellular vesicles on neuronal protection and functional recovery in the rat model of middle cerebral artery occlusion"],"prefix":"10.1002","volume":"38","author":[{"given":"Marzieh","family":"Mahdavipour","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gholamreza","family":"Hassanzadeh","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Tehran 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