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Hirudin has beneficial effects in ischemic stroke and possesses antioxidant and anti\u2010inflammatory properties. Therefore, we investigated the biological functions of hirudin and its related mechanisms in cerebral ischemia. The ischemia\u2010like conditions were induced by transient middle cerebral artery occlusion (MCAO). To investigate hirudin roles, intracerebroventricular injection of 10\u2009U hirudin was given to the rats. Cognitive and motor functions were examined by beam walking and Morris water maze tests. 2,3,5\u2010triphenyl tetrazolium chloride\u2010stained brain sections were used to measure infarct volume. Oxidative stress was determined by assessment of oxidative stress markers. The proliferated cells were labeled by BrdU and Nestin double staining. Western blotting was performed to measure protein levels. Hirudin administration improved cognitive and motor deficits post\u2010ischemia. Hirudin reduced brain infarction and neurological damage in MCAO\u2010subjected rats. Hirudin alleviated oxidative stress and enhanced neurogenesis in ischemic rats. Hirudin facilitated the promotion of phosphorylation of extracellular signal\u2010regulated kinase (ERK) 1\/2 and serine\u2010threonine kinase. In sum, hirudin alleviates cognitive deficits by attenuating oxidative stress and promoting hippocampal neurogenesis through the regulation of ERK1\/2 and serine\u2010threonine kinase in MCAO\u2010subjected rats.<\/jats:p>","DOI":"10.1111\/neup.12897","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:48:01Z","timestamp":1678841281000},"page":"362-372","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Intracerebral hirudin injection alleviates cognitive impairment and oxidative stress and promotes hippocampal neurogenesis in rats subjected to cerebral ischemia"],"prefix":"10.1111","volume":"43","author":[{"given":"Xianfeng","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University  Wuhan 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