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The aim of the present study was to determine the neuroprotective effects of hydroxychloroquine (HCQ) and the timing of its administration in cerebral ischemia\/reperfusion (I\/R) in rats. A global I\/R model was used, and HCQ was administered in either pre\u2010 or post\u2010treatment doses of 25 and 50\u2009mg\/kg. Effects of HCQ on infarct size, histological changes, oxidative stress, and learning and memory were evaluated. Phospho\u2010AMPK and SQSTM1\/p62 protein levels were also measured to elucidate the possible mechanisms involved. HCQ in both pre\u2010 (at doses of 25 and 50\u2009mg\/kg) or post\u2010treatment (at a dose of 50\u2009mg\/kg) protocols reduces brain infarct size and histopathological changes and improves learning and memory after cerebral I\/R. Pre\u2010treatment with HCQ reduced AMPK activity with no significant effect on SQSTM1\/p62 increment. Post\u2010treatment with HCQ increased AMPK activity and SQSTM1\/p62 protein levels. Our results show the neuroprotective effects of HCQ on cerebral I\/R through the reduction in infarct size, histopathological changes, and improvement in memory and learning functions. Moreover, AMPK and autophagy may play a role in this protective effect.<\/jats:p>","DOI":"10.1111\/fcp.12856","type":"journal-article","created":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T14:53:19Z","timestamp":1669474399000},"page":"589-598","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pre\u2010treatment or post\u2010treatment with hydroxychloroquine demonstrates neuroprotective effects in cerebral ischemia\/reperfusion"],"prefix":"10.1111","volume":"37","author":[{"given":"Shabnam","family":"Babataheri","sequence":"first","affiliation":[{"name":"Experimental and Applied Pharmaceutical Sciences Research Center Urmia University of Medical Sciences  Urmia Iran"},{"name":"Department of Pharmacology and Toxicology, School of Pharmacy Urmia University of Medical Sciences  Urmia 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