{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:58:24Z","timestamp":1790618304895,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Melatonin has shown neuroprotective potential in various models of cerebrovascular diseases, but its effects on mitophagy in vascular dementia (VaD) induced by chronic cerebral hypoperfusion (CCH) remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eighteen adult male Sprague\u2013Dawley rats underwent bilateral common carotid artery occlusion (BCCAO) to induce CCH. Animals were randomly assigned to three groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096 per group): sham\u2010operated controls, BCCAO model animals receiving vehicle injection, and BCCAO animals treated with daily melatonin (10\u2009mg\/kg, intraperitoneally for 14\u2009days). Cognitive performance was evaluated using the Morris water maze. Regional cerebral blood flow (rCBF) was measured with high\u2010resolution laser Doppler imaging. Mitophagy was assessed via Western blot analysis of LC3BII\/I, TOMM20, COX IV, caspase\u20103, and immunofluorescence colocalization of LC3B with TOMM20 in the hippocampal CA1 subfield.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BCCAO rats exhibited significant cognitive deficits in the Morris water maze, along with persistently reduced rCBF. BCCAO also induced a significant upregulation of hippocampal mitophagy, as indicated by an elevated LC3BII\/I, decreased TOMM20 and COX IV levels, and increased colocalization of TOMM20 and LC3B immunofluorescence signals. Caspase\u20103 expression was markedly higher in the BCCAO group. Melatonin treatment improved rCBF recovery at day\u200914, mitigated the spatial learning and memory impairments, decreased the LC3BII\/I, increased mitochondrial protein markers (TOMM20, COX IV), reduced the colocalization of TOMM20 and LC3B puncta, and attenuated caspase\u20103 levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that CCH in the VaD model induces excessive hippocampal mitophagy and cognitive impairment. The cognitive improvement observed with melatonin treatment is closely correlated with restored cerebral perfusion and attenuated mitophagic activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71141","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:59:48Z","timestamp":1788447588000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melatonin Improves Cognitive Function and Suppresses Excessive Mitophagy in Rats With Vascular Dementia"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3209-6409","authenticated-orcid":false,"given":"Si\u2010jia","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Neurology, Headache Center The First Hospital of Shanxi Medical University  Taiyuan 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