{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:05:26Z","timestamp":1753862726101,"version":"3.41.2"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"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":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Intracranial aneurysms (IAs) are relatively common cerebrovascular anomalies. Melatonin could modulate inflammatory and offers neuroprotective effects, and its role in IA has not been fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An elastase\u2010induced IA mouse model was constructed and melatonin (150\u00a0mg\/kg) was administered to investigate its therapeutic effects on IA. Aneurysm formation was observed by bromophenol blue gelatin perfusion, and the pathology changes in IA mice were examined using hematoxylin\u2010eosin (HE) staining. The potential mechanisms of melatonin treatment of IA were explored using western blot, enzyme\u2010linked immunosorbent, real\u2010time qPCR, immunohistochemistry, and flow cytometry. An H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010reduced human brain vascular smooth muscle cells (HBVSMC) injury model was also constructed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The formation of aneurysms was observed in the circle of Willis in the IA mice. Melatonin treatment alleviated the thinning of blood vessel walls and disruption of the internal elastic lamina in IA mice. The levels of Bcl\u20102 were significantly increased and Bax and cleaved caspase\u20103 were decreased in IA mice with melatonin treatment, suggesting reduced apoptosis. Furthermore, melatonin reduced levels of interleukin (IL)\u20101\u03b2, IL\u20106, and tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) in IA mice. The H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010reduced HBVSMCs model showed consistent results. Melatonin reduced levels of kr\u00fcppel\u2010like factor 6 (KLF6) in IA mice. Importantly, melatonin significantly reduced levels of regulatory T cells (Treg), hypoxia\u2010inducible factor (HIF)\u20101\u03b1, nuclear factor interleukin 3\u2010regulated (NFIL3), TCDD\u2010inducible poly\u2010ADP\u2010ribose polymerase (TIPARP), and increased levels of monocytes in IA mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Melatonin mitigates IA injury by modulating immune cells and hypoxia\u2010related factors. These findings provide an exploratory foundation for therapeutic strategies in IA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.70371","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T16:39:00Z","timestamp":1741019940000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia\u2010Related Factors in a Mouse Model of Elastase\u2010Induced Intracranial Aneurysm"],"prefix":"10.1002","volume":"15","author":[{"family":"NarenYa","sequence":"first","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Anhui Medical University  Hefei Anhui Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurology Suzhou Hospital of Anhui Medical University  Suzhou Anhui Province 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