{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T13:11:07Z","timestamp":1789305067146,"version":"build-2803163510"},"reference-count":72,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271296"],"award-info":[{"award-number":["82271296"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Mid\u2010gestational sevoflurane exposure may induce notable long\u2010term neurocognitive impairment in offspring. This study was designed to investigate the role and potential mechanism of ferroptosis in developmental neurotoxicity induced by sevoflurane in the second trimester.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant rats on day 13 of gestation (G13) were treated with or without 3.0% sevoflurane, Ferrostatin\u20101 (Fer\u20101), PD146176, or Ku55933 on three consecutive days. Mitochondrial morphology, ferroptosis\u2010relative proteins, malondialdehyde (MDA) levels, total iron content, and glutathione peroxidase 4 (GPX4) activities were measured. Hippocampal neuronal development in offspring was also examined. Subsequently, 15\u2010lipoxygenase 2 (15LO2)\u2010phosphatidylethanolamine binding protein 1 (PEBP1) interaction and expression of Ataxia telangiectasia mutated (ATM) and its downstream proteins were also detected. Furthermore, Morris water maze (MWM) and Nissl's staining were applied to estimate the long\u2010term neurotoxic effects of sevoflurane.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ferroptosis mitochondria were observed after maternal sevoflurane exposures. Sevoflurane elevated MDA and iron levels while inhibiting GPX4 activity, and resultant long\u2010term learning and memory dysfunction, which were alleviated by Fer\u20101, PD146176, and Ku55933. Sevoflurane could enhance 15LO2\u2010PEBP1 interaction and activate ATM and its downstream P53\/SAT1 pathway, which might be attributed to excessive p\u2010ATM nuclear translocation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study proposes that 15LO2\u2010mediated ferroptosis might contribute to neurotoxicity induced by maternal sevoflurane anesthesia during the mid\u2010trimester in the offspring and its mechanism may be ascribed to hyperactivation of ATM and enhancement of 15LO2\u2010PEBP1 interaction, indicating a potential therapeutic target for ameliorating sevoflurane\u2010induced neurotoxicity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14236","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T05:50:10Z","timestamp":1686203410000},"page":"2972-2985","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Multiple sevoflurane exposures during 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