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Some patients develop ischemia and reperfusion (I\/R) injury after <jats:styled-content style=\"fixed-case\">CEA<\/jats:styled-content>. This study was designed to investigate the neuroprotective effects of melatonin on I\/R injury in both rats and humans. To this end, 36 male rats were evaluated, and a double\u2010blind randomized controlled trial (<jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>) including 60 patients was performed. A rat model of middle cerebral artery occlusion was used to mimic cerebral I\/R. After 2\u00a0hour of occlusion and 24\u00a0hour of reperfusion, blood samples and brain tissues were harvested for further assessments. Compared with the vehicle treatment, melatonin decreased the expression of nuclear factor \u03ba light\u2010chain\u2010enhancer of activated B cells (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB) and S100 calcium\u2010binding protein \u03b2 (S100\u03b2) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and markedly increased the expression of nuclear erythroid 2\u2010related factor 2 (Nrf2), superoxide dismutase (<jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content>), catalase (<jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>), and glutathione peroxidase (<jats:styled-content style=\"fixed-case\">GP<\/jats:styled-content>x) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). The participants in the <jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content> took 6\u00a0mg\/d melatonin orally from 3\u00a0days before surgery to 3\u00a0days after surgery. Blood samples were drawn at the following times: baseline; pre\u2010anesthesia; carotid reconstruction completion; and 6, 24, and 72\u00a0hour after <jats:styled-content style=\"fixed-case\">CEA<\/jats:styled-content>. Compared with the oral placebo treatment, melatonin decreased the expression of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB, tumor necrosis factor\u2010\u03b1, interleukin\u20106 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106), and S100\u03b2 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and increased the expression of Nrf2, <jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> CAT<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">GP<\/jats:styled-content>x (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) in patients after <jats:styled-content style=\"fixed-case\">CEA<\/jats:styled-content>. Our findings suggested that melatonin could ameliorate brain I\/R injury after <jats:styled-content style=\"fixed-case\">CEA<\/jats:styled-content> and that this outcome was essentially due to the antioxidant and anti\u2010inflammatory effects of melatonin.<\/jats:p>","DOI":"10.1111\/jpi.12521","type":"journal-article","created":{"date-parts":[[2018,8,11]],"date-time":"2018-08-11T07:10:21Z","timestamp":1533971421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["The protective effect of melatonin on brain ischemia and reperfusion in rats and humans: In vivo assessment and a randomized controlled trial"],"prefix":"10.1111","volume":"65","author":[{"given":"Zhewei","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing 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