{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:58:24Z","timestamp":1787162304265,"version":"build-2736575974"},"reference-count":35,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Neurosci"],"abstract":"<jats:p>&lt;p&gt;Introduction: Sevoflurane is an extensively used anesthetic for pediatric patients; however, numerous studies showed that sevoflurane (SEVO) may cause long-term neurodevelopmental toxicity. Dexmedetomidine (DEX) has been shown to be protective against SEVO-induced neurotoxicity, but the mechanism remains unclear. The effects and mechanisms of different DEX administration routes on SEVO-induced neurotoxicity and long-term cognitive defects were determined and further investigated the role of sex in these processes. Methods: Male and female Sprague Dawley rats at postnatal day 7 (PND7) received an intraperitoneal injection of DEX (10 \u03bcg\/kg) before or after exposure to 2.5% SEVO for 6 h, or before and after SEVO exposure. The respiratory and mortality rates of the pups were recorded during anesthesia. Neuroapoptosis was evaluated by TdT-mediated dUTP nick-end labeling staining. Immunohistochemistry and immunofluorescence were employed to detect the expression of caspase-3 in neuronal cells and neurons. The expression of GSK-3\u03b2 and DISC1 was determined by Western blotting or RT-qPCR. Morris water maze (MWM) test was used to evaluate the learning and memory ability of rats until they were 3 weeks and 5 weeks old. Results: Compared with the control group, exposure to 2.5% SEVO resulted in increased neuroapoptosis and decreased the expression of DISC1 at levels of mRNA and protein and phosphorylated GSK-3\u03b2 in the developing brain. SEVO exposure during critical neurodevelopmental periods could cause persistent cognitive defects in adolescent male and female rats and inhibited DISC1 and phosphorylated GSK-3\u03b2 protein expression. The neurotoxic impacts of SEVO were lessened by the administration of DEX (10 \u03bcg\/kg) before or after exposure. Conclusion: Our findings suggest that DEX (10 \u03bcg\/kg) mitigates the neurotoxic effects of SEVO on the developing rat brain as well as postnatal cognitive defects by regulating the DISC1\/GSK-3\u03b2 signaling. &lt;\/p&gt;<\/jats:p>","DOI":"10.1159\/000542114","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T12:00:54Z","timestamp":1729512054000},"page":"193-205","source":"Crossref","is-referenced-by-count":3,"title":["Dexmedetomidine Alleviates the Long-Term Neurodevelopmental Toxicity Induced by Sevoflurane in the Developing Brain"],"prefix":"10.1159","volume":"47","author":[{"given":"Ting-Ting","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei-Fei","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Hua","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Ren","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2016.10.008"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002232"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1097\/01.anes.0000344728.34332.5d"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105685"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.01.031"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.6288.1"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2021.01.024"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02629-x"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2018.05.014"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.4097\/kjae.2017.70.6.642"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2021.08.028"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000005268"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2023.110809"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.08.044"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aex219"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2020.03.014"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aet057"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.12.044"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000001527"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2870"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.12182\/20210360601"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2015.11.001"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.48"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3182834d5d"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2022.113996"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1021\/cr000110o"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-8993(01)03005-0"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1086\/425586"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1113\/JP272187"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11676"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2017.01.001"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aex222"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200611000-00012"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6268"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2017.10.014"}],"container-title":["Developmental 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