{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T20:51:10Z","timestamp":1794257470495,"version":"4.9.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple sevoflurane exposures may damage the developing brain. The neuroprotective function of dexmedetomidine has been widely confirmed in animal experiments and human studies. However, the effect of dexmedetomidine on the glymphatic system has not been clearly studied. We hypothesized that dexmedetomidine could alleviate sevoflurane-induced circulatory dysfunction of the glymphatic system in young mice. Six-day-old C57BL\/6 mice were exposed to 3% sevoflurane for 2\u2009h daily, continuously for 3 days. Intraperitoneal injection of either normal saline or dexmedetomidine was administered before every anaesthesia. Meanwhile the circulatory function of glymphatic system was detected by tracer injection at P8 and P32. On P30-P32, behavior tests including open field test, novel object recognition test, and Y-maze test were conducted. Primary astrocyte cultures were established and treated with the PI3K activator 740Y-P, dexmedetomidine, and small interfering RNA (siRNA) to silence \u0394FosB. We propose for the first time that multiple exposure to sevoflurane induces circulatory dysfunction of the glymphatic system in young mice. Dexmedetomidine improves the circulatory capacity of the glymphatic system in young mice following repeated exposure to sevoflurane through the PI3K\/AKT\/\u0394FosB\/AQP4 signaling pathway, and enhances their long-term learning and working memory abilities.<\/jats:p>","DOI":"10.1038\/s41419-024-06845-w","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T13:03:01Z","timestamp":1719320581000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Dexmedetomidine improves the circulatory dysfunction of the glymphatic system induced by sevoflurane through the PI3K\/AKT\/\u0394FosB\/AQP4 pathway in young mice"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9399-6953","authenticated-orcid":false,"given":"Shuying","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weishu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gehua","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyang","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghua","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Hermenean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0781-5694","authenticated-orcid":false,"given":"Jun","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3959-9570","authenticated-orcid":false,"given":"Baoman","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5732-3806","authenticated-orcid":false,"given":"Yan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3757-5767","authenticated-orcid":false,"given":"Xu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"6845_CR1","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1056\/NEJMp1700196","volume":"376","author":"DB Andropoulos","year":"2017","unstructured":"Andropoulos DB, Greene MF. Anesthesia and developing brains\u2014implications of the FDA warning. N Engl J Med. 2017;376:905\u20137. https:\/\/doi.org\/10.1056\/NEJMp1700196.","journal-title":"N Engl J Med"},{"key":"6845_CR2","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/S0140-6736(18)32485-1","volume":"393","author":"ME McCann","year":"2019","unstructured":"McCann ME, de Graaff JC, Dorris L, Disma N, Withington D, Bell G, et al. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial. Lancet. 2019;393:664\u201377. https:\/\/doi.org\/10.1016\/S0140-6736(18)32485-1.","journal-title":"Lancet"},{"key":"6845_CR3","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0140-6736(15)00608-X","volume":"387","author":"Davidson","year":"2016","unstructured":"Davidson, Disma AJ, de Graaff N, Withington DE JC, Dorris L, Bell G, et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016;387:239\u201350. https:\/\/doi.org\/10.1016\/S0140-6736(15)00608-X.","journal-title":"Lancet"},{"key":"6845_CR4","doi-asserted-by":"publisher","first-page":"2312.","DOI":"10.1001\/jama.2016.6967","volume":"315","author":"LS Sun","year":"2016","unstructured":"Sun LS, Li G, Miller TLK, Salorio C, Byrne MW, Bellinger DC, et al. Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood. JAMA. 2016;315:2312. https:\/\/doi.org\/10.1001\/jama.2016.6967.","journal-title":"JAMA"},{"key":"6845_CR5","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1097\/ALN.0000000000002232","volume":"129","author":"DO Warner","year":"2018","unstructured":"Warner DO, Zaccariello MJ, Katusic SK, Schroeder DR, Hanson AC, Schulte PJ, et al. Neuropsychological and behavioral outcomes after exposure of young children to procedures requiring general anesthesia. Anesthesiology. 2018;129:89\u2013105. https:\/\/doi.org\/10.1097\/ALN.0000000000002232.","journal-title":"Anesthesiology"},{"key":"6845_CR6","doi-asserted-by":"publisher","first-page":"147ra111.","DOI":"10.1126\/scitranslmed.3003748","volume":"4","author":"JJ Iliff","year":"2012","unstructured":"Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med. 2012;4:147ra111. https:\/\/doi.org\/10.1126\/scitranslmed.3003748.","journal-title":"Sci Transl Med"},{"key":"6845_CR7","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1126\/science.1240514","volume":"340","author":"M Nedergaard","year":"2013","unstructured":"Nedergaard M. Garbage Truck of the Brain. Science. 2013;340:1529\u201330. https:\/\/doi.org\/10.1126\/science.1240514.","journal-title":"Science"},{"key":"6845_CR8","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/j.clinthera.2021.01.024","volume":"43","author":"C Apai","year":"2021","unstructured":"Apai C, Shah R, Tran K, Pandya SS. Anesthesia and the developing brain: a review of sevoflurane-induced neurotoxicity in pediatric populations. Clin Ther. 2021;43:762\u201378. https:\/\/doi.org\/10.1016\/j.clinthera.2021.01.024.","journal-title":"Clin Ther"},{"key":"6845_CR9","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav5447","volume":"5","author":"LM Hablitz","year":"2019","unstructured":"Hablitz LM, Vinitsky HS, Sun Q, Staeger FF, Sigurdsson B, Mortensen KN, et al. Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia. Sci Adv. 2019;5:eaav5447. https:\/\/doi.org\/10.1126\/sciadv.aav5447.","journal-title":"Sci Adv"},{"key":"6845_CR10","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.neuropharm.2015.07.005","volume":"99","author":"V Vialou","year":"2015","unstructured":"Vialou V, Thibault M, Kaska S, Cooper S, Gajewski P, Eagle A, et al. Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress. Neuropharmacology. 2015;99:28\u201337. https:\/\/doi.org\/10.1016\/j.neuropharm.2015.07.005.","journal-title":"Neuropharmacology"},{"key":"6845_CR11","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.ejphar.2014.10.034","volume":"753","author":"EJ Nestler","year":"2015","unstructured":"Nestler EJ. FosB: a transcriptional regulator of stress and antidepressant responses. Eur J Pharmacol. 2015;753:66\u201372. https:\/\/doi.org\/10.1016\/j.ejphar.2014.10.034.","journal-title":"Eur J Pharmacol"},{"key":"6845_CR12","doi-asserted-by":"publisher","first-page":"2955","DOI":"10.1016\/j.celrep.2019.02.050","volume":"26","author":"AS Munk","year":"2019","unstructured":"Munk AS, Wang W, B\u00e8chet NB, Eltanahy AM, Cheng AX, Sigurdsson B, et al. PDGF-B is required for development of the glymphatic system. Cell Rep. 2019;26:2955\u201369. https:\/\/doi.org\/10.1016\/j.celrep.2019.02.050.","journal-title":"Cell Rep"},{"key":"6845_CR13","doi-asserted-by":"publisher","first-page":"5912","DOI":"10.1038\/s41380-020-00992-0","volume":"26","author":"J Wu","year":"2021","unstructured":"Wu J, Carlock C, Shim J, Moreno-Gonzalez I, Glass WN, Ross A, et al. Requirement of brain interleukin33 for aquaporin4 expression in astrocytes and glymphatic drainage of abnormal tau. Mol Psychiatry. 2021;26:5912\u201324. https:\/\/doi.org\/10.1038\/s41380-020-00992-0.","journal-title":"Mol Psychiatry"},{"key":"6845_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000475928","volume":"43","author":"DB Andropoulos","year":"2018","unstructured":"Andropoulos DB. Effect of anesthesia on the developing brain: infant and fetus. Fetal Diagn Ther. 2018;43:1\u201311. https:\/\/doi.org\/10.1159\/000475928.","journal-title":"Fetal Diagn Ther"},{"key":"6845_CR15","doi-asserted-by":"publisher","first-page":"2724","DOI":"10.3390\/jcm9092724","volume":"9","author":"M Mahmoud","year":"2020","unstructured":"Mahmoud M, Barbi E, Mason KP. Dexmedetomidine: what\u2019s new for pediatrics? A narrative review. J Clin Med. 2020;9:2724 https:\/\/doi.org\/10.3390\/jcm9092724.","journal-title":"J Clin Med"},{"key":"6845_CR16","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jconrel.2019.05.005","volume":"304","author":"TO Lilius","year":"2019","unstructured":"Lilius TO, Blomqvist K, Hauglund NL, Liu G, St\u00e6ger FF, B\u00e6rentzen S, et al. Dexmedetomidine enhances glymphatic brain delivery of intrathecally administered drugs. J Control Release. 2019;304:29\u201338. https:\/\/doi.org\/10.1016\/j.jconrel.2019.05.005.","journal-title":"J Control Release"},{"key":"6845_CR17","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1097\/ALN.0000000000001888","volume":"127","author":"H Benveniste","year":"2017","unstructured":"Benveniste H, Lee H, Ding F, Sun Q, Al-Bizri E, Makaryus R, et al. Anesthesia with dexmedetomidine and low-dose isoflurane increases solute transport via the glymphatic pathway in rat brain when compared with high-dose isoflurane. Anesthesiology. 2017;127:976\u201388. https:\/\/doi.org\/10.1097\/ALN.0000000000001888.","journal-title":"Anesthesiology"},{"key":"6845_CR18","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.2147\/NDT.S169099","volume":"14","author":"Y Xiao","year":"2018","unstructured":"Xiao Y, Zhou L, Tu Y, Li Y, Liang Y, Zhang X, et al. Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K\/Akt signaling pathway. Neuropsychiatr Dis Treat. 2018;14:2191\u2013206. https:\/\/doi.org\/10.2147\/NDT.S169099.","journal-title":"Neuropsychiatr Dis Treat"},{"key":"6845_CR19","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.biopha.2017.08.125","volume":"95","author":"M Shen","year":"2017","unstructured":"Shen M, Wang S, Wen X, Han XR, Wang YJ, Zhou XM, et al. Dexmedetomidine exerts neuroprotective effect via the activation of the PI3K\/Akt\/mTOR signaling pathway in rats with traumatic brain injury. Biomed Pharmacother. 2017;95:885\u201393. https:\/\/doi.org\/10.1016\/j.biopha.2017.08.125.","journal-title":"Biomed Pharmacother"},{"key":"6845_CR20","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1007\/s11064-015-1581-6","volume":"40","author":"NA Jessen","year":"2015","unstructured":"Jessen NA, Munk ASF, Lundgaard I, Nedergaard M. The glymphatic system: a beginner\u2019s guide. Neurochem Res. 2015;40:2583\u201399. https:\/\/doi.org\/10.1007\/s11064-015-1581-6.","journal-title":"Neurochem Res"},{"key":"6845_CR21","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1038\/nn.4661","volume":"20","author":"J Lisman","year":"2017","unstructured":"Lisman J, Buzsaki G, Eichenbaum H, Nadel L, Ranganath C, Redish AD. Viewpoints: how the hippocampus contributes to memory, navigation and cognition. Nat Neurosci. 2017;20:1434\u201347. https:\/\/doi.org\/10.1038\/nn.4661.","journal-title":"Nat Neurosci"},{"key":"6845_CR22","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/s41586-024-07132-6","volume":"627","author":"MH Murdock","year":"2024","unstructured":"Murdock MH, Yang CY, Sun N, Pao PC, Blanco-Duque C, Kahn MC, et al. Multisensory gamma stimulation promotes glymphatic clearance of amyloid. Nature. 2024;627:149\u201356. https:\/\/doi.org\/10.1038\/s41586-024-07132-6.","journal-title":"Nature"},{"key":"6845_CR23","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.1093\/brain\/awaa179","volume":"143","author":"IF Harrison","year":"2020","unstructured":"Harrison IF, Ismail O, Machhada A, Colgan N, Ohene Y, Nahavandi P, et al. Impaired glymphatic function and clearance of tau in an Alzheimer\u2019s disease model. Brain. 2020;143:2576\u201393. https:\/\/doi.org\/10.1093\/brain\/awaa179.","journal-title":"Brain"},{"key":"6845_CR24","doi-asserted-by":"publisher","first-page":"16180","DOI":"10.1523\/JNEUROSCI.3020-14.2014","volume":"34","author":"JJ Iliff","year":"2014","unstructured":"Iliff JJ, Chen MJ, Plog BA, Zeppenfeld DM, Soltero M, Yang L, et al. Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J Neurosci. 2014;34:16180\u201393. https:\/\/doi.org\/10.1523\/JNEUROSCI.3020-14.2014.","journal-title":"J Neurosci"},{"key":"6845_CR25","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1007\/s00401-010-0679-9","volume":"119","author":"GK Gouras","year":"2010","unstructured":"Gouras GK, Tampellini D, Takahashi RH, Capetillo-Zarate E. Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer\u2019s disease. Acta Neuropathol. 2010;119:523\u201341. https:\/\/doi.org\/10.1007\/s00401-010-0679-9.","journal-title":"Acta Neuropathol"},{"key":"6845_CR26","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.neuron.2018.06.003","volume":"99","author":"A Ittner","year":"2018","unstructured":"Ittner A, Ittner LM. Dendritic Tau in Alzheimer\u2019s disease. Neuron. 2018;99:13\u201327. https:\/\/doi.org\/10.1016\/j.neuron.2018.06.003.","journal-title":"Neuron"},{"key":"6845_CR27","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1038\/nm1782","volume":"14","author":"GM Shankar","year":"2008","unstructured":"Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, et al. Amyloid-beta protein dimers isolated directly from Alzheimer\u2019s brains impair synaptic plasticity and memory. Nat Med. 2008;14:837\u201342. https:\/\/doi.org\/10.1038\/nm1782.","journal-title":"Nat Med"},{"key":"6845_CR28","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s00018-021-04062-8","volume":"79","author":"M Stazi","year":"2021","unstructured":"Stazi M, Lehmann S, Sakib MS, Pena-Centeno T, Buschgens L, Fischer A, et al. Long-term caffeine treatment of Alzheimer mouse models ameliorates behavioural deficits and neuron loss and promotes cellular and molecular markers of neurogenesis. Cell Mol Life Sci. 2021;79:55. https:\/\/doi.org\/10.1007\/s00018-021-04062-8.","journal-title":"Cell Mol Life Sci"},{"key":"6845_CR29","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02182-3","volume":"18","author":"XY Sun","year":"2021","unstructured":"Sun XY, Li LJ, Dong QX, Zhu J, Huang YR, Hou SJ, et al. Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer\u2019s disease. J Neuroinflammation. 2021;18:131. https:\/\/doi.org\/10.1186\/s12974-021-02182-3.","journal-title":"J Neuroinflammation"},{"key":"6845_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109194","volume":"35","author":"K Dore","year":"2021","unstructured":"Dore K, Carrico Z, Alfonso S, Marino M, Koymans K, Kessels HW, et al. PSD-95 protects synapses from beta-amyloid. Cell Rep. 2021;35:109194. https:\/\/doi.org\/10.1016\/j.celrep.2021.109194.","journal-title":"Cell Rep"},{"key":"6845_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-019-0525-3","volume":"9","author":"J Sun","year":"2019","unstructured":"Sun J, Xu J, Ling Y, Wang F, Gong T, Yang C, et al. Fecal microbiota transplantation alleviated Alzheimer\u2019s disease-like pathogenesis in APP\/PS1 transgenic mice. Transl Psychiatry. 2019;9:189 https:\/\/doi.org\/10.1038\/s41398-019-0525-3.","journal-title":"Transl Psychiatry"},{"key":"6845_CR32","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1750-1326-9-48","volume":"9","author":"S Tu","year":"2014","unstructured":"Tu S, Okamoto S, Lipton SA, Xu H. Oligomeric Abeta-induced synaptic dysfunction in Alzheimer\u2019s disease. Mol Neurodegener. 2014;9:48. https:\/\/doi.org\/10.1186\/1750-1326-9-48.","journal-title":"Mol Neurodegener"},{"key":"6845_CR33","doi-asserted-by":"publisher","first-page":"3051","DOI":"10.1111\/j.1742-4658.2010.07719.x","volume":"277","author":"E Pham","year":"2010","unstructured":"Pham E, Crews L, Ubhi K, Hansen L, Adame A, Cartier A, et al. Progressive accumulation of amyloid-beta oligomers in Alzheimer\u2019s disease and in amyloid precursor protein transgenic mice is accompanied by selective alterations in synaptic scaffold proteins. FEBS J. 2010;277:3051\u201367. https:\/\/doi.org\/10.1111\/j.1742-4658.2010.07719.x.","journal-title":"FEBS J"},{"key":"6845_CR34","doi-asserted-by":"publisher","first-page":"10191","DOI":"10.1523\/JNEUROSCI.3432-04.2004","volume":"24","author":"PN Lacor","year":"2004","unstructured":"Lacor PN, Buniel MC, Chang L, Fernandez SJ, Gong Y, Viola KL, et al. Synaptic targeting by Alzheimer\u2019s-related amyloid beta oligomers. J Neurosci. 2004;24:10191\u201310200. https:\/\/doi.org\/10.1523\/JNEUROSCI.3432-04.2004.","journal-title":"J Neurosci"},{"key":"6845_CR35","doi-asserted-by":"publisher","first-page":"4390","DOI":"10.3390\/ijms23084390","volume":"23","author":"AM Levy","year":"2022","unstructured":"Levy AM, Gomez-Puertas P, Tumer Z. Neurodevelopmental disorders associated with PSD-95 and its interaction partners. Int J Mol Sci. 2022;23:4390. https:\/\/doi.org\/10.3390\/ijms23084390.","journal-title":"Int J Mol Sci"},{"key":"6845_CR36","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.pnpbp.2017.11.016","volume":"82","author":"AA Coley","year":"2018","unstructured":"Coley AA, Gao WJ. PSD95: A synaptic protein implicated in schizophrenia or autism? Prog Neuropsychopharmacol Biol Psychiatry. 2018;82:187\u201394. https:\/\/doi.org\/10.1016\/j.pnpbp.2017.11.016.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"6845_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45971-w","volume":"9","author":"AA Coley","year":"2019","unstructured":"Coley AA, Gao WJ. PSD-95 deficiency disrupts PFC-associated function and behavior during neurodevelopment. Sci Rep. 2019;9:9486 https:\/\/doi.org\/10.1038\/s41598-019-45971-w.","journal-title":"Sci Rep"},{"key":"6845_CR38","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1213\/ANE.0000000000001942","volume":"124","author":"Y Xia","year":"2017","unstructured":"Xia Y, Xu H, Jia C, Hu X, Kang Y, Yang X, et al. Tanshinone IIA attenuates sevoflurane neurotoxicity in neonatal mice. Anesth Analg. 2017;124:1244\u201352. https:\/\/doi.org\/10.1213\/ANE.0000000000001942.","journal-title":"Anesth Analg"},{"key":"6845_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1006175","volume":"16","author":"L Zhong","year":"2022","unstructured":"Zhong L, Ma X, Niu Y, Zhang L, Xue Z, Yan J, et al. Sevoflurane exposure may cause dysplasia of dendritic spines and result in fine motor dysfunction in developing mouse through the PI3K\/AKT\/mTOR pathway. Front Neurosci. 2022;16:1006175 https:\/\/doi.org\/10.3389\/fnins.2022.1006175.","journal-title":"Front Neurosci"},{"key":"6845_CR40","doi-asserted-by":"publisher","first-page":"428","DOI":"10.3109\/00952990.2014.933840","volume":"40","author":"JK Ruffle","year":"2014","unstructured":"Ruffle JK. Molecular neurobiology of addiction: what\u2019s all the (Delta)FosB about? Am J Drug Alcohol Abuse. 2014;40:428\u201337. https:\/\/doi.org\/10.3109\/00952990.2014.933840.","journal-title":"Am J Drug Alcohol Abuse"},{"key":"6845_CR41","doi-asserted-by":"publisher","first-page":"11042","DOI":"10.1073\/pnas.191352698","volume":"98","author":"EJ Nestler","year":"2001","unstructured":"Nestler EJ, Barrot M, Self DW. DeltaFosB: a sustained molecular switch for addiction. Proc Natl Acad Sci USA. 2001;98:11042\u20136. https:\/\/doi.org\/10.1073\/pnas.191352698.","journal-title":"Proc Natl Acad Sci USA"},{"key":"6845_CR42","doi-asserted-by":"publisher","first-page":"305","DOI":"10.2174\/156800907780809741","volume":"7","author":"X Zhang","year":"2007","unstructured":"Zhang X, Jin B, Huang C. The PI3K\/Akt pathway and its downstream transcriptional factors as targets for chemoprevention. Curr Cancer Drug Targets. 2007;7:305\u201316. https:\/\/doi.org\/10.2174\/156800907780809741.","journal-title":"Curr Cancer Drug Targets"},{"key":"6845_CR43","doi-asserted-by":"publisher","first-page":"e40070","DOI":"10.7554\/eLife.40070","volume":"7","author":"H Mestre","year":"2018","unstructured":"Mestre H, Hablitz LM, Xavier AL, Feng W, Zou W, Pu T, et al. Aquaporin-4-dependent glymphatic solute transport in the rodent brain. Elife. 2018;7:e40070 https:\/\/doi.org\/10.7554\/eLife.40070.","journal-title":"Elife"},{"key":"6845_CR44","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.lfs.2019.02.024","volume":"221","author":"X Gao","year":"2019","unstructured":"Gao X, Ming J, Liu S, Lai B, Fang F, Cang J. Sevoflurane enhanced the clearance of A\u03b21-40 in hippocampus under surgery via up-regulating AQP-4 expression in astrocyte. Life Sci. 2019;221:143\u201351. https:\/\/doi.org\/10.1016\/j.lfs.2019.02.024.","journal-title":"Life Sci"},{"key":"6845_CR45","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1097\/ALN.0000000000000477","volume":"122","author":"LG Amrock","year":"2015","unstructured":"Amrock LG, Starner ML, Murphy KL, Baxter MG. Long-term effects of single or multiple neonatal sevoflurane exposures on rat hippocampal ultrastructure. Anesthesiology. 2015;122:87\u201395. https:\/\/doi.org\/10.1097\/ALN.0000000000000477.","journal-title":"Anesthesiology"},{"key":"6845_CR46","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.tins.2009.08.002","volume":"32","author":"MV Sofroniew","year":"2009","unstructured":"Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 2009;32:638\u201347. https:\/\/doi.org\/10.1016\/j.tins.2009.08.002.","journal-title":"Trends Neurosci"},{"key":"6845_CR47","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jare.2023.03.004","volume":"56","author":"X Si","year":"2024","unstructured":"Si X, Dai S, Fang Y, Tang J, Wang Z, Li Y, et al. Matrix metalloproteinase-9 inhibition prevents aquaporin-4 depolarization-mediated glymphatic dysfunction in Parkinson\u2019s disease. J Adv Res. 2024;56:125\u201336. https:\/\/doi.org\/10.1016\/j.jare.2023.03.004.","journal-title":"J Adv Res"},{"key":"6845_CR48","doi-asserted-by":"publisher","first-page":"3434","DOI":"10.7150\/thno.81951","volume":"13","author":"S Feng","year":"2023","unstructured":"Feng S, Wu C, Zou P, Deng Q, Chen Z, Li M, et al. High-intensity interval training ameliorates Alzheimer\u2019s disease-like pathology by regulating astrocyte phenotype-associated AQP4 polarization. Theranostics. 2023;13:3434\u201350. https:\/\/doi.org\/10.7150\/thno.81951.","journal-title":"Theranostics"},{"key":"6845_CR49","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/jcbfm.2013.30","volume":"33","author":"Z Ren","year":"2013","unstructured":"Ren Z, Iliff JJ, Yang L, Yang J, Chen X, Chen MJ, et al. \u2018Hit & Run\u2019 model of closed-skull traumatic brain injury (TBI) reveals complex patterns of post-traumatic AQP4 dysregulation. J Cereb Blood Flow Metab. 2013;33:834\u201345. https:\/\/doi.org\/10.1038\/jcbfm.2013.30.","journal-title":"J Cereb Blood Flow Metab"},{"key":"6845_CR50","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1213\/ANE.0000000000005268","volume":"132","author":"M Sun","year":"2021","unstructured":"Sun M, Dong Y, Li M, Zhang Y, Liang F, Zhang J, et al. Dexmedetomidine and clonidine attenuate sevoflurane-induced tau phosphorylation and cognitive impairment in young mice via alpha-2 adrenergic receptor. Anesth Analg. 2021;132:878\u201389. https:\/\/doi.org\/10.1213\/ANE.0000000000005268.","journal-title":"Anesth Analg"},{"key":"6845_CR51","doi-asserted-by":"publisher","first-page":"391","DOI":"10.3390\/biomedicines11020391","volume":"11","author":"N Jimenez-Tellez","year":"2023","unstructured":"Jimenez-Tellez N, Pehar M, Iqbal F, Casas-Ortiz A, Rice T, Syed NI. Dexmedetomidine pre-treatment of neonatal rats prevents sevoflurane-induced deficits in learning and memory in the adult animals. Biomedicines. 2023;11:391. https:\/\/doi.org\/10.3390\/biomedicines11020391.","journal-title":"Biomedicines"},{"key":"6845_CR52","doi-asserted-by":"publisher","first-page":"710","DOI":"10.7150\/thno.19154","volume":"8","author":"C Gakuba","year":"2018","unstructured":"Gakuba C, Gaberel T, Goursaud S, Bourges J, Di Palma C, Quenault A, et al. General anesthesia inhibits the activity of the \u201cglymphatic system. Theranostics. 2018;8:710\u201322. https:\/\/doi.org\/10.7150\/thno.19154.","journal-title":"Theranostics"},{"key":"6845_CR53","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.1241224","volume":"342","author":"L Xie","year":"2013","unstructured":"Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342:373\u20137. https:\/\/doi.org\/10.1126\/science.1241224.","journal-title":"Science"},{"key":"6845_CR54","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.bja.2021.08.028","volume":"127","author":"Y Yang","year":"2021","unstructured":"Yang Y, Liang F, Gao J, Dong Y, Zhang Y, Yang G, et al. Testosterone attenuates sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice. Br J Anaesth. 2021;127:929\u201341. https:\/\/doi.org\/10.1016\/j.bja.2021.08.028.","journal-title":"Br J Anaesth"},{"key":"6845_CR55","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1097\/NEN.0b013e31821284e9","volume":"70","author":"N Lunardi","year":"2011","unstructured":"Lunardi N, Hucklenbruch C, Latham JR, Scarpa J, Jevtovic-Todorovic V. Isoflurane impairs immature astroglia development in vitro: the role of actin cytoskeleton. J Neuropathol Exp Neurol. 2011;70:281\u201391. https:\/\/doi.org\/10.1097\/NEN.0b013e31821284e9.","journal-title":"J Neuropathol Exp Neurol"},{"key":"6845_CR56","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1416-5","volume":"10","author":"YB Sun","year":"2019","unstructured":"Sun YB, Zhao H, Mu DL, Zhang W, Cui J, Wu L, et al. Dexmedetomidine inhibits astrocyte pyroptosis and subsequently protects the brain in in vitro and in vivo models of sepsis. Cell Death Dis. 2019;10:167. https:\/\/doi.org\/10.1038\/s41419-019-1416-5.","journal-title":"Cell Death Dis"},{"key":"6845_CR57","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/s42003-021-02047-8","volume":"4","author":"Y Dong","year":"2021","unstructured":"Dong Y, Liang F, Huang L, Fang F, Yang G, Tanzi RE, et al. The anesthetic sevoflurane induces tau trafficking from neurons to microglia. Commun Biol. 2021;4:560. https:\/\/doi.org\/10.1038\/s42003-021-02047-8.","journal-title":"Commun Biol"},{"key":"6845_CR58","doi-asserted-by":"publisher","first-page":"139","DOI":"10.3389\/fphar.2017.00139","volume":"8","author":"Y Li","year":"2017","unstructured":"Li Y, Shen R, Wen G, Ding R, Du A, Zhou J, et al. Effects of ketamine on levels of inflammatory cytokines IL-6, IL-1beta, and TNF-alpha in the hippocampus of mice following acute or chronic administration. Front Pharmacol. 2017;8:139 https:\/\/doi.org\/10.3389\/fphar.2017.00139.","journal-title":"Front Pharmacol"},{"key":"6845_CR59","doi-asserted-by":"publisher","first-page":"e0253902","DOI":"10.1371\/journal.pone.0253902","volume":"16","author":"G Ghamkharinejad","year":"2021","unstructured":"Ghamkharinejad G, Marashi SH, Foolad F, Javan M, Fathollahi Y. Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits. PLoS One. 2021;16:e0253902. https:\/\/doi.org\/10.1371\/journal.pone.0253902.","journal-title":"PLoS One"},{"key":"6845_CR60","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02393-2","volume":"19","author":"S Liu","year":"2022","unstructured":"Liu S, Fan M, Xu JX, Yang LJ, Qi CC, Xia QR, et al. Exosomes derived from bone-marrow mesenchymal stem cells alleviate cognitive decline in AD-like mice by improving BDNF-related neuropathology. J Neuroinflammation. 2022;19:35. https:\/\/doi.org\/10.1186\/s12974-022-02393-2.","journal-title":"J Neuroinflammation"},{"key":"6845_CR61","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/ab.21481","volume":"39","author":"P Mesa-Gresa","year":"2013","unstructured":"Mesa-Gresa P, Perez-Martinez A, Redolat R. Environmental enrichment improves novel object recognition and enhances agonistic behavior in male mice. Aggress Behav. 2013;39:269\u201379. https:\/\/doi.org\/10.1002\/ab.21481","journal-title":"Aggress Behav"},{"key":"6845_CR62","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1002\/ana.24271","volume":"76","author":"BT Kress","year":"2014","unstructured":"Kress BT, Iliff JJ, Xia M, Wang M, Wei HS, Zeppenfeld D, et al. Impairment of paravascular clearance pathways in the aging brain. Ann Neurol. 2014;76:845\u201361. https:\/\/doi.org\/10.1002\/ana.24271.","journal-title":"Ann Neurol"},{"key":"6845_CR63","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1007\/s00213-018-5147-6","volume":"236","author":"F Wei","year":"2019","unstructured":"Wei F, Song J, Zhang C, Lin J, Xue R, Shan LD, et al. Chronic stress impairs the aquaporin-4-mediated glymphatic transport through glucocorticoid signaling. Psychopharmacology. 2019;236:1367\u201384. https:\/\/doi.org\/10.1007\/s00213-018-5147-6.","journal-title":"Psychopharmacology"},{"key":"6845_CR64","doi-asserted-by":"publisher","first-page":"9353","DOI":"10.1523\/JNEUROSCI.0127-11.2011","volume":"31","author":"AM Reeves","year":"2011","unstructured":"Reeves AM, Shigetomi E, Khakh BS. Bulk loading of calcium indicator dyes to study astrocyte physiology: key limitations and improvements using morphological maps. J Neurosci. 2011;31:9353\u20138. https:\/\/doi.org\/10.1523\/JNEUROSCI.0127-11.2011.","journal-title":"J Neurosci"},{"key":"6845_CR65","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1089\/neu.2015.4339","volume":"34","author":"AN Hoffman","year":"2017","unstructured":"Hoffman AN, Paode PR, May HG, Ortiz JB, Kemmou S, Lifshitz J, et al. Early and persistent dendritic hypertrophy in the basolateral amygdala following experimental diffuse traumatic brain injury. J Neurotrauma. 2017;34:213\u20139. https:\/\/doi.org\/10.1089\/neu.2015.4339.","journal-title":"J Neurotrauma"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06845-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06845-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06845-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T13:03:26Z","timestamp":1719320606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06845-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,25]]},"references-count":65,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["6845"],"URL":"https:\/\/doi.org\/10.1038\/s41419-024-06845-w","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,25]]},"assertion":[{"value":"18 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All experimental protocols were approved by the Animal Care and Use Committee of China Medical University, with the approval number CMU2020307, and followed the ARRIVE reporting guidelines. Every effort was made to minimize the number of animals used and to reduce their pain and suffering.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"448"}}