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Previous studies showed that melatonin preserves <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1 expression in neuronal cells of newborn rats after hypoxia\u2013ischemia. However, the definite role of <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1 in the protective effect of melatonin against cerebral <jats:styled-content style=\"fixed-case\">IRI<\/jats:styled-content> in adult has not been explored. In this study, the brain of adult mice was subjected to <jats:styled-content style=\"fixed-case\">IRI<\/jats:styled-content>. Prior to this procedure, the mice were given intraperitoneal with or without the <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1 inhibitor, <jats:styled-content style=\"fixed-case\">EX<\/jats:styled-content>527. Melatonin conferred a cerebral\u2010protective effect, as shown by reduced infarct volume, lowered brain edema, and increased neurological scores. The melatonin\u2010induced upregulation of <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1 was also associated with an increase in the anti\u2010apoptotic factor, Bcl2, and a reduction in the pro\u2010apoptotic factor Bax. Moreover, melatonin resulted in a well\u2010preserved mitochondrial membrane potential, mitochondrial Complex I activity, and mitochondrial cytochrome <jats:italic>c<\/jats:italic> level while it reduced cytosolic cytochrome <jats:italic>c<\/jats:italic> level. However, the melatonin\u2010elevated mitochondrial function was reversed by <jats:styled-content style=\"fixed-case\">EX<\/jats:styled-content>527 treatment. In summary, our results demonstrate that melatonin treatment attenuates cerebral <jats:styled-content style=\"fixed-case\">IRI<\/jats:styled-content> by reducing <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\u2010induced mitochondrial dysfunction through the activation of <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1 signaling.<\/jats:p>","DOI":"10.1111\/jpi.12193","type":"journal-article","created":{"date-parts":[[2014,11,17]],"date-time":"2014-11-17T10:41:19Z","timestamp":1416220879000},"page":"61-70","source":"Crossref","is-referenced-by-count":219,"title":["Melatonin prevents cell death and mitochondrial dysfunction via a <scp>SIRT<\/scp>1\u2010dependent mechanism during ischemic\u2010stroke in mice"],"prefix":"10.1111","volume":"58","author":[{"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Xijing Hospital The Fourth Military Medical University Xi'an China"},{"name":"Department of 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