en Related Fields Related Fields مقاله کامل Full Length/Original Article <strong>Background:</strong>&nbsp;Ischemic stroke, as a health problem caused by the reduced blood supply to the brain, can lead to the neuronal death. The number of reliable therapies for stroke is limited. Mesenchymal stem cells (MSCs) exhibit therapeutic achievement. A major limitation of MSC application in cell therapy is the short survival span. MSCs affect target tissues through the secretion of many paracrine agents including extracellular vesicles (EVs). This study aimed to investigate the effect of human umbilical cord perivascular cells (HUCPVCs)-derived EVs on apoptosis, functional recovery, and neuroprotection. <strong>Methods: </strong>Ischemia was induced by middle cerebral artery occlusion (MCAO) in male Wistar rats. Animals were classified into sham, MCAO, MCAO + HUCPVC, and MCAO + EV groups. Treatments began at two hours after ischemia. Expressions of apoptotic-related proteins (BAX/BCl-2 [B-cell lymphoma-2] and caspase-3 and -9), the amount of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, neuronal density (microtubule-associated protein 2 [MAP2]), and dead neurons (Nissl staining) were assessed on day seven post MCAO. <strong>Results: </strong>Administration of EVs improved the sensorimotor function (<em>p < </em>0.001) and reduced the apoptotic rate of Bax/Bcl-2 ratio (<em>p < </em>0.001), as well as caspases and TUNEL-positive cells (<em>p </em>< 0.001) in comparison to the MCAO group. EV treatment also reduced the number of dead neurons and increased the number of MAP2⁺ cells in the ischemic boundary zone (<em>p </em>< 0.001), as compared to the MCAO group. <strong>Conclusion:&nbsp;</strong> Our findings showed that HUCPVCs-derived EVs are more effective than their mother&rsquo;s cells in improving neural function, possibly via the regulation of apoptosis in the ischemic rats. The strategy of cell-free extracts is, thus, helpful in removing the predicaments surrounding cell therapy in targeting brain diseases. Apoptosis, Extracellular vesicles, Ischemia, Middle cerebral artery 347 360 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-1-835&slc_lang=en&sid=1 Elham Seifali 0000-0003-0945-5821 No Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Gholamreza Hassanzadeh 0000-0003-0724-6479 No Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Marzieh Mahdavipour 0000-0002-1417-500X No Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Keywan Mortezaee 0000-0003-2004-3465 No Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran Ashraf Moini 0000-0002-5074-2286 No Department of Gynecology and Obstetrics, School of Medicine, Tehran University of Medical Science, Tehran, Iran Leila Satarian 0000-0002-5068-5031 No Department of Brain and Cognitive Science, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran Faezeh Shekari 0000-0001-6026-5412 No Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran Abdoreza Nazari 0000-0002-8630-6208 No Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran Shabnam Movassaghi 0000-0002-0320-9569 No Department of Anatomy and cognitive neuroscience, School of Medicine, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran Mohammad Akbari 0000-0002-2478-7755 Yes Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran