{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:07:14Z","timestamp":1758931634495,"version":"3.44.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Innovation Team Scientific Research Projects of Health Commission of Sichuan Province, China","award":["24CXTD18","24CXTD18","24CXTD18","24CXTD18","24CXTD18","24CXTD18"],"award-info":[{"award-number":["24CXTD18","24CXTD18","24CXTD18","24CXTD18","24CXTD18","24CXTD18"]}]},{"name":"Key Project of In-Hospital Scientific and Technological Innovation Fund of Sichuan Provincial Women\u2019s and Children\u2019s Hospital","award":["20240103","20240103","20240103","20240103","20240103","20240103"],"award-info":[{"award-number":["20240103","20240103","20240103","20240103","20240103","20240103"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Neonatal exposure to sevoflurane has been associated with neurodevelopmental impairments. However, the mechanisms underlying increased susceptibility to stress-related neurological disorders remain unclear. This study aimed to investigate the brain vulnerability after repeated neonatal sevoflurane exposure in rats to future traumatic stress exposure.P5 male Sprague - Dawley rats were exposed to 3% sevoflurane for 2\u00a0h daily from P6 to P8. Bumetanide, an NKCC1 inhibitor, was administered intraperitoneally before sevoflurane exposure. The expression of NKCC1 in the hippocampus at P8 was detected by reverse transcription -polymerase chain reaction and Western blot analysis. The brain vulnerability to stress exposure was assessed at P14-20 by conditioned fear traumatic stress model. The stress response was assessed by measuring serum corticosterone level. Primary hippocampal neurons of neonatal rat were cultured in vitro and exposed to sevoflurane with or without bumetanide pretreatment. The growth activity, intracellular LDH enzyme activity, ROS levels and apoptosis of hippocampal neurons were determined. Repeated neonatal sevoflurane exposure in rats enhanced serum corticosterone secretion after fear conditioning training and induced deficits in fear extinction training and recall.Pretreatment with bumetanide reversed these effects. In cultured primary neonatal rat hippocampal neurons, sevoflurane exposure enhanced the expression of NKCC1, increased the markers of neuronal cytotoxicity and downregulated the expression of Noggin, Drebrin and MAP2. In contrast, pretreatment with NKCC1 inhibitor bumetanide attenuated these adverse effects in vitro. Our results suggest repeated neonatal sevoflurane exposure enhances stress-related neurological susceptibility in rats by upregulating NKCC1, highlighting NKCC1 as a potential therapeutic target for anesthesia-induced neurodevelopmental vulnerability.<\/jats:p>","DOI":"10.1038\/s41598-025-18584-9","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T11:14:18Z","timestamp":1758885258000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal sevoflurane exposure enhances stress-related neurological susceptibility via NKCC1 modulation"],"prefix":"10.1038","volume":"15","author":[{"given":"Bi-ying","family":"Yuan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-hui","family":"Shan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-hai","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-qi","family":"Gan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben-zhen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"18584_CR1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0140-6736(15)00608-X","volume":"387","author":"AJ Davidson","year":"2016","unstructured":"Davidson, A. 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This study was reported in accordance with the ARRIVE guidelines ().","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"33150"}}