{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:57:09Z","timestamp":1790092629169,"version":"4.0.1"},"reference-count":63,"publisher":"SAGE Publications","issue":"10-12","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>This study aims to investigate whether melatonin (MLT) exerts protective effects against cognitive impairment following exertional heat stroke (EHS) by modulating ferroportin (Fpn) to alleviate hippocampal ferroptosis and neuroinflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Following EHS, genes such as\n                      <jats:italic toggle=\"yes\">Mt1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Mt2<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Trf<\/jats:italic>\n                      were notably upregulated in the hippocampal tissue, whereas genes such as\n                      <jats:italic toggle=\"yes\">Slc40a1<\/jats:italic>\n                      (encoding Fpn 1) and\n                      <jats:italic toggle=\"yes\">Il33<\/jats:italic>\n                      were downregulated. Kyoto Encyclopedia of Genes and Genomes analysis implicated ferroptosis as a dominant. MLT significantly ameliorated learning and memory deficits observed in EHS mice. This treatment also modulated ferroptosis markers, such as Fpn, xCT, ferritin H, and glutathione peroxidase 4, reduced hippocampal iron overload, and decreased the secretion of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-\u03b1 (TNF-\u03b1). Furthermore, MLT treatment reduced oxidative stress and lipid peroxidation and mitigated mitochondrial and neuronal damage in the hippocampal tissue. Strikingly, conditional Fpn knockout abolished MLT\u2019s benefits: Fpn-cKO\u2009+\u2009MLT mice showed persistent iron accumulation, elevated IL-6 and TNF-\u03b1, and failed cognitive recovery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>Our study reveals that MLT prevents EHS-induced neurodegeneration by enhancing Fpn-dependent iron efflux, a mechanism that concurrently resolves hippocampal iron overload, suppresses ferroptosis, and dampens neuroinflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Our findings indicate that MLT mitigates EHS-related cognitive impairment by restoring hippocampal iron homeostasis and suppressing neuroinflammation, primarily through Fpn-dependent mechanisms.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      43, 509\u2013527.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864251363577","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T20:15:23Z","timestamp":1758917723000},"page":"509-527","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Melatonin Ameliorates Cognitive Impairment Following Exertional Heat Stroke by Inhibiting Ferroptosis and Neuroinflammation"],"prefix":"10.1177","volume":"43","author":[{"given":"Xiaochen","family":"Wang","sequence":"first","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin, People\u2019s Republic of China."},{"name":"Department of Critical Care Medicine, First Medical Center of Chinese PLA General Hospital, Beijing, People\u2019s Republic of China."},{"name":"Department of Nephrology, First Medical Center of Chinese PLA General 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