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Empagliflozin, a sodium\u2013glucose cotransporter 2 (SGLT 2) inhibitor, was shown to effectively reduce hyperglycemia and glucotoxicity besides improving glycemic control in diabetics. Therefore, the present study was conducted to investigate the neuroprotective effect of empagliflozin against cerebral I\/R injury in hyperglycemic rats. Hyperglycemia was induced by streptozotocin (55\u00a0mg\/kg), and transient cerebral I\/R was induced by bilateral common carotid occlusion for 30\u00a0min followed by 24\u2010h reperfusion. Either empagliflozin (10\u00a0mg\/kg; i.p.) or gliclazide (2\u00a0mg\/kg, p.o.) was administered at 1 and 24\u00a0h after reperfusion. Treatment with empagliflozin showed a significant amelioration of behavioral\/neurological functions and histopathological changes observed in brain tissues of hyperglycemic rats subjected to cerebral I\/R injury. Comparable to gliclazide, empagliflozin decreased cerebral infarct volume along with suppression of cerebral oxidative stress, inflammatory, and apoptotic markers in brain tissues of hyperglycemic I\/R\u2010injured rats. These findings suggested that empagliflozin can significantly alleviate neuronal damage resulting from global I\/R injury induced in hyperglycemic rats. The proposed neuroprotective effect of empagliflozin may be attributed to its glycemic control effect and related antioxidant, anti\u2010inflammatory, and antiapoptotic effects.<\/jats:p>","DOI":"10.1111\/fcp.12548","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T11:38:57Z","timestamp":1582025937000},"page":"548-558","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Empagliflozin attenuates transient cerebral ischemia\/reperfusion injury in hyperglycemic rats via repressing oxidative\u2013inflammatory\u2013apoptotic pathway"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-5555","authenticated-orcid":false,"given":"Entesar F.","family":"Amin","sequence":"first","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine Minia University El\u2010Minia 61511 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7481-2656","authenticated-orcid":false,"given":"Rehab A.","family":"Rifaai","sequence":"additional","affiliation":[{"name":"Department of Histology Faculty of Medicine Minia University El\u2010Minia 61511 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3770-7128","authenticated-orcid":false,"given":"Rania G.","family":"Abdel\u2010latif","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy Minia University El\u2010Minia 61511 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,10]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"3","article-title":"The global burden of disease brain summit","volume":"52","author":"Feigin V.","year":"2019","journal-title":"Neuroepidemiology"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2009.231"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.519926"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16671730"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-014-0365-7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000195175.29487.30"},{"key":"e_1_2_7_8_1","first-page":"CD005346","article-title":"Insulin for glycaemic control in acute ischaemic stroke","volume":"1","author":"Bellolio M.F.","year":"2014","journal-title":"Cochrane Database Syst. 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