{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:27:17Z","timestamp":1791228437595,"version":"4.1.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2017ZC0083"],"award-info":[{"award-number":["2017ZC0083"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BBraun Investigation Fund of Anesthesia Science","award":["2013"],"award-info":[{"award-number":["2013"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuromol Med"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p>Although there is an increment in stroke burden in the world, stroke therapeutic strategies are still extremely limited to a minority of patients. We previously demonstrated that dexmedetomidine (DEX) protects against focal cerebral ischemia via inhibiting neurons autophagy. Nevertheless, the role of DEX in regulating astrocytes autophagic status in oxygen\u2013glucose deprivation, a condition that mimics cerebral ischemia, is still unknown. In this study, we have shown that DEX and DEX\u2009+\u2009RAPA (autophagy inducer) increased viability and reduced apoptosis of primary astrocytes in oxygen\u2013glucose deprivation (OGD) model compared with DEX\u2009+\u20093-methyladenine (3-MA) (autophagy inhibitor). DEX induced the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1, while reduced the expression of p62 in primary cultured astrocytes through induction of autophagy. In addition, DEX enhanced the expression of tuberous sclerosis complex 2 (TSC2) in primary cultured astrocytes, while reduced the expression of mammalian target of rapamycin (mTOR). In conclusion, our study suggests that DEX exerts a neuroprotection against OGD-induced astrocytes injury via activation of astrocytes autophagy by regulating the TSC2\/mTOR signaling pathway, which provides a new insight into the mechanisms of DEX treatment for acute ischemic injury.<\/jats:p>","DOI":"10.1007\/s12017-019-08576-0","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T20:48:43Z","timestamp":1572036523000},"page":"210-217","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Dexmedetomidine Protects Against Oxygen\u2013Glucose Deprivation-Induced Injury Through Inducing Astrocytes Autophagy via TSC2\/mTOR Pathway"],"prefix":"10.1007","volume":"22","author":[{"given":"Chen","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4464-812X","authenticated-orcid":false,"given":"Cong","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,25]]},"reference":[{"issue":"7598","key":"8576_CR1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/nature17623","volume":"532","author":"MA Anderson","year":"2016","unstructured":"Anderson, M. A., Burda, J. E., et al. (2016). Astrocyte scar formation aids central nervous system axon regeneration. Nature,532(7598), 195\u2013200.","journal-title":"Nature"},{"issue":"2","key":"8576_CR2","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1159\/000457877","volume":"41","author":"J Bao","year":"2017","unstructured":"Bao, J., Li, G., et al. (2017). Contribution of p62 to phenotype transition of coronary arterial myocytes with defective autophagy. Cellular Physiology and Biochemistry,41(2), 555\u2013568.","journal-title":"Cellular Physiology and Biochemistry"},{"issue":"3","key":"8576_CR3","doi-asserted-by":"publisher","first-page":"366","DOI":"10.4161\/auto.6.3.11261","volume":"6","author":"S Carloni","year":"2010","unstructured":"Carloni, S., Girelli, S., et al. (2010). Activation of autophagy and Akt\/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia. Autophagy,6(3), 366\u2013377.","journal-title":"Autophagy"},{"issue":"1","key":"8576_CR4","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1074\/jbc.M110.159046","volume":"286","author":"A Carriere","year":"2011","unstructured":"Carriere, A., Romeo, Y., et al. (2011). ERK1\/2 phosphorylate raptor to promote ras-dependent activation of mTOR complex 1 (mTORC1). Journal of Biological Chemistry,286(1), 567\u2013577.","journal-title":"Journal of Biological Chemistry"},{"issue":"3","key":"8576_CR5","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1097\/ALN.0b013e318164ca81","volume":"108","author":"S Dahmani","year":"2008","unstructured":"Dahmani, S., Paris, A., et al. (2008). Dexmedetomidine increases hippocampal phosphorylated extracellular signal-regulated protein kinase 1 and 2 content by an alpha 2-adrenoceptor-independent mechanism: evidence for the involvement of imidazoline I1 receptors. Anesthesiology,108(3), 457\u2013466.","journal-title":"Anesthesiology"},{"issue":"5","key":"8576_CR6","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1097\/ALN.0b013e318286cf36","volume":"118","author":"V Degos","year":"2013","unstructured":"Degos, V., Charpentier, T. L., et al. (2013). Neuroprotective effects of dexmedetomidine against glutamate agonist-induced neuronal cell death are related to increased astrocyte brain-derived neurotrophic factor expression. Anesthesiology,118(5), 1123\u20131132.","journal-title":"Anesthesiology"},{"issue":"1","key":"8576_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1734-1140(12)70725-9","volume":"64","author":"B Gabryel","year":"2012","unstructured":"Gabryel, B., Kost, A., et al. (2012). Neuronal autophagy in cerebral ischemia\u2013a potential target for neuroprotective strategies? Pharmacological Reports,64(1), 1\u201315.","journal-title":"Pharmacological Reports"},{"issue":"8","key":"8576_CR8","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1002\/cbin.10793","volume":"41","author":"B Gabryel","year":"2017","unstructured":"Gabryel, B., Kost, A., et al. (2017). AMP-activated protein kinase is involved in induction of protective autophagy in astrocytes exposed to oxygen-glucose deprivation. Cell Biology International,41(8), 928\u2013931.","journal-title":"Cell Biology International"},{"issue":"3","key":"8576_CR9","doi-asserted-by":"publisher","first-page":"R153","DOI":"10.1186\/cc10283","volume":"15","author":"J Gu","year":"2011","unstructured":"Gu, J., Sun, P., et al. (2011). Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Critical Care,15(3), R153.","journal-title":"Critical Care"},{"issue":"7613","key":"8576_CR10","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nature18928","volume":"535","author":"K Hayakawa","year":"2016","unstructured":"Hayakawa, K., Esposito, E., et al. (2016). Transfer of mitochondria from astrocytes to neurons after stroke. Nature,535(7613), 551\u2013555.","journal-title":"Nature"},{"issue":"14","key":"8576_CR11","doi-asserted-by":"publisher","first-page":"1766","DOI":"10.1002\/glia.21047","volume":"58","author":"SB Janen","year":"2010","unstructured":"Janen, S. B., Chaachouay, H., et al. (2010). Autophagy is activated by proteasomal inhibition and involved in aggresome clearance in cultured astrocytes. Glia,58(14), 1766\u20131774.","journal-title":"Glia"},{"key":"8576_CR12","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.neulet.2017.04.011","volume":"649","author":"E Kim","year":"2017","unstructured":"Kim, E., Kim, H. C., et al. (2017). Dexmedetomidine confers neuroprotection against transient global cerebral ischemia\/reperfusion injury in rats by inhibiting inflammation through inactivation of the TLR-4\/NF-kappaB pathway. Neuroscience Letters,649, 20\u201327.","journal-title":"Neuroscience Letters"},{"issue":"3","key":"8576_CR13","doi-asserted-by":"publisher","first-page":"e00045","DOI":"10.1002\/prp2.45","volume":"2","author":"J Lempiainen","year":"2014","unstructured":"Lempiainen, J., Finckenberg, P., et al. (2014). Dexmedetomidine preconditioning ameliorates kidney ischemia\u2013reperfusion injury. Pharmacology Research & Perspectives,2(3), e00045.","journal-title":"Pharmacology Research & Perspectives"},{"issue":"4","key":"8576_CR14","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/S1534-5807(04)00099-1","volume":"6","author":"B Levine","year":"2004","unstructured":"Levine, B., & Klionsky, D. J. (2004). Development by self-digestion: Molecular mechanisms and biological functions of autophagy. Developmental Cell,6(4), 463\u2013477.","journal-title":"Developmental Cell"},{"issue":"3","key":"8576_CR15","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1038\/sj.jcbfm.9600546","volume":"28","author":"L Li","year":"2008","unstructured":"Li, L., Lundkvist, A., et al. (2008). Protective role of reactive astrocytes in brain ischemia. Journal of Cerebral Blood Flow and Metabolism,28(3), 468\u2013481.","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"key":"8576_CR16","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3389\/fncel.2017.00197","volume":"11","author":"C Luo","year":"2017","unstructured":"Luo, C., Ouyang, M., et al. (2017). Dexmedetomidine protects mouse brain from ischemia-reperfusion injury via inhibiting neuronal autophagy through up-regulating HIF-1\u03b1. Frontiers in Cellular Neuroscience,11, 197.","journal-title":"Frontiers in Cellular Neuroscience"},{"issue":"1\u20132","key":"8576_CR17","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.ejphar.2004.08.044","volume":"502","author":"D Ma","year":"2004","unstructured":"Ma, D., Hossain, M., et al. (2004). Dexmedetomidine produces its neuroprotective effect via the \u03b12A-adrenoceptor subtype. European Journal of Pharmacology,502(1\u20132), 87\u201397.","journal-title":"European Journal of Pharmacology"},{"issue":"1","key":"8576_CR18","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1097\/CCM.0000000000000673","volume":"43","author":"JL Mu","year":"2015","unstructured":"Mu, J. L., Lee, A., et al. (2015). Pharmacologic agents for the prevention and treatment of delirium in patients undergoing cardiac surgery. Critical Care Medicine,43(1), 194\u2013204.","journal-title":"Critical Care Medicine"},{"key":"8576_CR19","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3389\/fnins.2018.00060","volume":"12","author":"MJ Perez-Alvarez","year":"2018","unstructured":"Perez-Alvarez, M. J., Villa, G. M., et al. (2018). Role of mTORC1 controlling proteostasis after brain ischemia. Front Neurosci,12, 60.","journal-title":"Front Neurosci"},{"issue":"4","key":"8576_CR20","doi-asserted-by":"publisher","first-page":"e0153097","DOI":"10.1371\/journal.pone.0153097","volume":"11","author":"A Pla","year":"2016","unstructured":"Pla, A., Pascual, M., et al. (2016). Autophagy constitutes a protective mechanism against ethanol toxicity in mouse astrocytes and neurons. PLoS ONE,11(4), e0153097.","journal-title":"PLoS ONE"},{"issue":"6","key":"8576_CR21","doi-asserted-by":"publisher","first-page":"738","DOI":"10.4161\/auto.6.6.12573","volume":"6","author":"AP Qin","year":"2010","unstructured":"Qin, A. P., Liu, C. F., et al. (2010). Autophagy was activated in injured astrocytes and mildly decreased cell survival following glucose and oxygen deprivation and focal cerebral ischemia. Autophagy,6(6), 738\u2013753.","journal-title":"Autophagy"},{"issue":"4","key":"8576_CR22","doi-asserted-by":"publisher","first-page":"422","DOI":"10.4161\/auto.5778","volume":"4","author":"A Rami","year":"2008","unstructured":"Rami, A., & Kogel, D. (2008). Apoptosis meets autophagy-like cell death in the ischemic penumbra: Two sides of the same coin? Autophagy,4(4), 422\u2013426.","journal-title":"Autophagy"},{"issue":"2","key":"8576_CR23","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/nrn2978","volume":"12","author":"S Robel","year":"2011","unstructured":"Robel, S., Berninger, B., et al. (2011). The stem cell potential of glia: Lessons from reactive gliosis. Nature Reviews Neuroscience,12(2), 88\u2013104.","journal-title":"Nature Reviews Neuroscience"},{"issue":"37","key":"8576_CR24","doi-asserted-by":"publisher","first-page":"13489","DOI":"10.1073\/pnas.0405659101","volume":"101","author":"PP Roux","year":"2004","unstructured":"Roux, P. P., Ballif, B. A., et al. (2004). Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proceedings of the National Academy of Sciences of the United States of America,101(37), 13489\u201313494.","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"5698","key":"8576_CR25","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1126\/science.1099993","volume":"306","author":"T Shintani","year":"2004","unstructured":"Shintani, T., & Klionsky, D. J. (2004). Autophagy in health and disease: A double-edged sword. Science,306(5698), 990\u2013995.","journal-title":"Science"},{"issue":"12","key":"8576_CR26","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.tins.2009.08.002","volume":"32","author":"MV Sofroniew","year":"2009","unstructured":"Sofroniew, M. V. (2009). Molecular dissection of reactive astrogliosis and glial scar formation. Trends in Neurosciences,32(12), 638\u2013647.","journal-title":"Trends in Neurosciences"},{"issue":"9","key":"8576_CR27","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1111\/1440-1681.12791","volume":"44","author":"Y Sun","year":"2017","unstructured":"Sun, Y., Jiang, C., et al. (2017). Dexmedetomidine protects mice against myocardium ischaemic\/reperfusion injury by activating an AMPK\/PI3K\/Akt\/eNOS pathway. Clinical and Experimental Pharmacology and Physiology,44(9), 946\u2013953.","journal-title":"Clinical and Experimental Pharmacology and Physiology"},{"issue":"8","key":"8576_CR28","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.4161\/auto.6.8.13427","volume":"6","author":"F Tian","year":"2010","unstructured":"Tian, F., Deguchi, K., et al. (2010). In vivo imaging of autophagy in a mouse stroke model. Autophagy,6(8), 1107\u20131114.","journal-title":"Autophagy"},{"issue":"1","key":"8576_CR29","doi-asserted-by":"publisher","first-page":"77","DOI":"10.4161\/auto.8.1.18274","volume":"8","author":"P Wang","year":"2012","unstructured":"Wang, P., Guan, Y. F., et al. (2012). Induction of autophagy contributes to the neuroprotection of nicotinamide phosphoribosyltransferase in cerebral ischemia. Autophagy,8(1), 77\u201387.","journal-title":"Autophagy"},{"issue":"9","key":"8576_CR30","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.4161\/auto.29203","volume":"10","author":"P Wang","year":"2014","unstructured":"Wang, P., Xu, T. Y., et al. (2014). ARRB1\/beta-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia. Autophagy,10(9), 1535\u20131548.","journal-title":"Autophagy"},{"key":"8576_CR31","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.brainres.2018.06.028","volume":"1698","author":"X Wu","year":"2018","unstructured":"Wu, X., Li, X., et al. (2018a). Hydrogen exerts neuroprotective effects on OGD\/R damaged neurons in rat hippocampal by protecting mitochondrial function via regulating mitophagy mediated by PINK1\/Parkin signaling pathway. Brain Research,1698, 89\u201398.","journal-title":"Brain Research"},{"issue":"2","key":"8576_CR32","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1002\/acn3.507","volume":"5","author":"M Wu","year":"2018","unstructured":"Wu, M., Zhang, H., et al. (2018b). Rapamycin prevents cerebral stroke by modulating apoptosis and autophagy in penumbra in rats. Annals of Clinical and Translational Neurology,5(2), 138\u2013146.","journal-title":"Annals of Clinical and Translational Neurology"},{"issue":"10","key":"8576_CR33","first-page":"761","volume":"38","author":"C Xie","year":"2015","unstructured":"Xie, C., Li, Y., et al. (2015). The effect of dexmedetomidine on autophagy and apoptosis in intestinal ischemia reperfusion-induced lung injury. Zhonghua Jie He He Hu Xi Za Zhi,38(10), 761\u2013764.","journal-title":"Zhonghua Jie He He Hu Xi Za Zhi"},{"issue":"5","key":"8576_CR34","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.neuint.2011.01.013","volume":"58","author":"M Yan","year":"2011","unstructured":"Yan, M., Dai, H., et al. (2011). Effects of dexmedetomidine on the release of glial cell line-derived neurotrophic factor from rat astrocyte cells. Neurochemistry International,58(5), 549\u2013557.","journal-title":"Neurochemistry International"},{"issue":"1","key":"8576_CR35","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/j.2042-7158.2011.01382.x","volume":"64","author":"F Zhang","year":"2012","unstructured":"Zhang, F., Ding, T., et al. (2012). Dexmedetomidine protects against oxygen-glucose deprivation-induced injury through the I2 imidazoline receptor-PI3K\/AKT pathway in rat C6 glioma cells. Journal of Pharmacy and Pharmacology,64(1), 120\u2013127.","journal-title":"Journal of Pharmacy and Pharmacology"},{"issue":"9","key":"8576_CR36","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.4161\/auto.25132","volume":"9","author":"X Zhang","year":"2013","unstructured":"Zhang, X., Yan, H., et al. (2013). Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. Autophagy,9(9), 1321\u20131333.","journal-title":"Autophagy"}],"container-title":["NeuroMolecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12017-019-08576-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12017-019-08576-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12017-019-08576-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T23:38:22Z","timestamp":1603496302000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12017-019-08576-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,25]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["8576"],"URL":"https:\/\/doi.org\/10.1007\/s12017-019-08576-0","relation":{},"ISSN":["1535-1084","1559-1174"],"issn-type":[{"value":"1535-1084","type":"print"},{"value":"1559-1174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,25]]},"assertion":[{"value":"6 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that there are no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"All animals used in present study were provided by the Southern Medical University Administrative Panel on Laboratory Animal Care and all animal experiments were carried out according to the guidelines of Animal Use and Care of Southern Medical University.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}