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The current study aimed to clarify the neuroprotective role of EPRO in middle carotid artery occlusion (MCAO)\u2010induced ischemic stroke in rats. Fifty\u2010six male Wistar rats were divided into four groups (<jats:italic>n<\/jats:italic>\u2009=\u200914 per group): sham\u2010operated group, sham receiving EPRO (60\u2009mg\/kg\/day, po) group, ischemia\u2013reperfusion (IR) group, and IR receiving EPRO (60\u2009mg\/kg\/day, po) group. MCAO led to a remarkable impairment in motor function together with stimulation of inflammatory and apoptotic pathways in the hippocampus of rats. After MCAO, the AT1 receptor in the brain was stimulated, resulting in activation of Janus kinase 2\/signal transducers and activators of transcription 3 signaling generating more neuroinflammatory milieu and destructive actions on the hippocampus. Augmentation of caspase\u20103 level by MCAO enhanced neuronal apoptosis synchronized with neurodegenerative effects of oxidative stress biomarkers. Pretreatment with EPRO opposed motor impairment and decreased oxidative and apoptotic mediators in the hippocampus of rats. The anti\u2010inflammatory activity of EPRO was revealed by downregulation of nuclear factor\u2010kappa B and tumor necrosis factor\u2010\u03b2 levels and (C\u2013X\u2013C motif) ligand 1 messenger RNA (mRNA) expression. Moreover, the study confirmed the role of EPRO against a unique pathway of hypoxia\u2010inducible factor\u20101\u03b1 and its subsequent inflammatory mediators. Furthermore, upregulation of caveolin\u20101 mRNA level was also observed along with decreased oxidative stress marker levels and brain edema. Therefore, EPRO showed neuroprotective effects in MCAO\u2010induced cerebral ischemia in rats via attenuation of oxidative, apoptotic, and inflammatory pathways.<\/jats:p>","DOI":"10.1002\/jbt.22796","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T06:18:59Z","timestamp":1620109139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Eprosartan: A closer insight into its neuroprotective activity in rats with focal cerebral ischemia\u2013reperfusion injury"],"prefix":"10.1002","volume":"35","author":[{"given":"Muhammad A. E.","family":"Saad","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Cairo University  Giza Egypt"},{"name":"School of Pharmacy New Giza University  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed I. 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