{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T02:48:32Z","timestamp":1780368512845,"version":"3.54.1"},"reference-count":70,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cerebral ischemia and diabetes mellitus (DM) are common diseases that often coexist and interact with each other. DM doubles the risk of ischemic stroke, and cerebral ischemia causes stress\u2010induced hyperglycemia. Most experimental stroke studies used healthy animals. Melatonin is neuroprotective against cerebral ischemia\u2013reperfusion injury (CIRI) in non\u2010DM, normoglycemic animals through anti\u2010oxidant effect, anti\u2010inflammation, and anti\u2010apoptosis. Previous studies have also reported a negative correlation between hyperglycemia and urinary melatonin metabolite.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The present study investigated the effects of type 1 DM (T1DM) on CIRI in rats and the role of melatonin against CIRI in T1DM animals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results revealed that T1DM aggravated CIRI, leading to greater weight loss, increased infarct volume, and worse neurological deficit. T1DM aggravated the post\u2010CIRI activation of nuclear factor kappa B (NF\u2010\u03baB) pathway and increase in pro\u2010apoptotic markers. A single intraperitoneal injection of melatonin at 10\u00a0mg\/kg given 30\u00a0min before ischemia onset attenuated CIRI in T1DM rats, resulting in less weight loss, decreased infarct volume, and milder neurological deficit when compared with the vehicle group. Melatonin treatment achieved anti\u2010inflammatory and anti\u2010apoptotic effects with reduced NF\u2010\u03baB pathway activation, reduced mitochondrial cytochrome C release, decreased calpain\u2010mediated spectrin breakdown product (SBDP), and decreased caspase\u20103\u2010mediated SBDP. The treatment also led to fewer iNOS+ cells, milder CD\u201068+ macrophage\/microglia infiltration, decreased TUNEL+ apoptotic cells, and better neuronal survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>T1DM aggravates CIRI. Melatonin treatment is neuroprotective against CIRI in T1DM rats via anti\u2010inflammatory and anti\u2010apoptotic effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.3118","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T14:23:37Z","timestamp":1686925417000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Melatonin mitigates type 1 diabetes\u2010aggravated cerebral ischemia\u2010reperfusion injury through anti\u2010inflammatory and anti\u2010apoptotic effects"],"prefix":"10.1002","volume":"13","author":[{"given":"Qian","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5448-5451","authenticated-orcid":false,"given":"Raymond Tak Fai","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong"},{"name":"Research Centre of Heart, Brain, Hormone &amp; Healthy Aging, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24220"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12144"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14\u2010S081"},{"key":"e_1_2_9_5_1","volume-title":"IDF Diabetes Atlas","author":"International Diabetes Federation","year":"2015"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(05)80182-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006\u20108993(97)01414\u20105"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.03.002"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.531632"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1179\/1743132815Y.0000000033"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010019\u20100118\u20108"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u2010079X.2007.00551.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.228762"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2016.116"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(18)31320\u20105"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166\u20102236(99)01401\u20100"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7219740"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12395"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12264"},{"key":"e_1_2_9_20_1","first-page":"3445","article-title":"Animal models of ischemic stroke and their application in clinical research","volume":"9","author":"Fluri F.","year":"2015","journal-title":"Drug Design, Development and Therapy"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176275"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u2010079X.2008.00615.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.621854"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1994.11.187"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12525"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2013.03.010"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0901217"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs232"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.130"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101799"},{"issue":"1","key":"e_1_2_9_31_1","first-page":"27","article-title":"Molecular and cellular mechanisms of cardiotoxicity","volume":"109","author":"Kang Y. 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