{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:10:59Z","timestamp":1784214659753,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Dexmedetomidine (DEX) is commonly employed as a sedative agent to attenuate sympathetic tone and reduce norepinephrine (NE) levels. In the context of stroke-associated pneumonia (SAP), which is believed to arise from heightened sympathetic nervous system activity and elevated NE release, the precise influence of DEX remains uncertain.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In this study, we generated an SAP model using middle cerebral artery occlusion (MCAO) and examined NE levels, immunological statuses in the brain and periphery, pneumonia symptoms, and extent of infarction. We aimed to determine the effects of DEX on SAP and explore the underlying. Despite its potential to reduce NE levels, DEX did not alleviate SAP symptoms or decrease the infarct area. Interestingly, DEX led to an increase in spleen size and spleen index. Furthermore, we observed a decrease in the CD3+ T cell population in both the blood and brain, but an increase in the spleen following DEX administration. The precise mechanism linking decreased CD3<jats:sup>+<\/jats:sup> T cells and DEX\u2019s role in SAP requires further investigation.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The clinical use of DEX in stroke patients should be approached with caution, considering its inability to alleviate SAP symptoms and reduce the infarct area. Further research is necessary to fully understand the relationship between decreased CD3<jats:sup>+<\/jats:sup> T cells and DEX\u2019s influence on SAP.<\/jats:p>","DOI":"10.3389\/fphar.2023.1203646","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T10:04:02Z","timestamp":1690970642000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["As an inhibitor of norepinephrine release, dexmedetomidine provides no improvement on stroke-associated pneumonia in mice"],"prefix":"10.3389","volume":"14","author":[{"given":"Miaomiao","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1111\/j.1600-6143.2005.00755.x","article-title":"The hemodynamic mechanisms of lung injury and systemic inflammatory response following brain death in the transplant donor","volume":"5","author":"Avlonitis","year":"2005","journal-title":"Am. J. Transpl."},{"key":"B2","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1177\/1747493018806196","article-title":"Frequency of post-stroke pneumonia: Systematic review and meta-analysis of observational studies","volume":"14","author":"Badve","year":"2019","journal-title":"Int. J. Stroke"},{"key":"B3","doi-asserted-by":"publisher","first-page":"6136105","DOI":"10.1155\/2020\/6136105","article-title":"Organ-protective effects and the underlying mechanism of dexmedetomidine","volume":"2020","author":"Bao","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"B4","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cellimm.2007.09.005","article-title":"Sympathetic modulation of immunity: Relevance to disease","volume":"252","author":"Bellinger","year":"2008","journal-title":"Cell Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/s0167-5699(98)01367-x","article-title":"Catecholaminergic suppression of immunocompetent cells","volume":"19","author":"Bergquist","year":"1998","journal-title":"Immunol. Today"},{"key":"B6","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1002\/ana.25073","article-title":"Stroke-induced chronic systolic dysfunction driven by sympathetic overactivity","volume":"82","author":"Bieber","year":"2017","journal-title":"Ann. Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1096\/fj.11-201640","article-title":"Anti-inflammatory effects of \u03b22 adrenergic receptor agonists in experimental acute lung injury","volume":"26","author":"Bosmann","year":"2012","journal-title":"FASEB J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1161\/01.STR.0000258346.68966.9d","article-title":"Infection after acute ischemic stroke: A manifestation of brain-induced immunodepression","volume":"38","author":"Chamorro","year":"2007","journal-title":"Stroke"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.3791\/2761","article-title":"Mouse model of middle cerebral artery occlusion","volume":"48","author":"Chiang","year":"2011","journal-title":"J. Vis. Exp."},{"key":"B10","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1111\/j.1348-0421.1992.tb02045.x","article-title":"Definition and application of a histopathological scoring scheme for an animal model of acute Mycoplasma pneumoniae pulmonary infection","volume":"36","author":"Cimolai","year":"1992","journal-title":"Microbiol. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s12974-021-02177-0","article-title":"Stroke-induced immunosuppression: Implications for the prevention and prediction of post-stroke infections","volume":"18","author":"Faura","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1212\/WNL.0b013e31823152b1","article-title":"Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke","volume":"77","author":"Finlayson","year":"2011","journal-title":"Neurology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.bja.2019.08.026","article-title":"Dexmedetomidine modulates neuroinflammation and improves outcome via alpha2-adrenergic receptor signaling after rat spinal cord injury","volume":"123","author":"Gao","year":"2019","journal-title":"Br. J. Anaesth."},{"key":"B14","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/s0006-8993(02)03368-1","article-title":"Temporal effects of left versus right middle cerebral artery occlusion on spleen lymphocyte subsets and mitogenic response in Wistar rats","volume":"955","author":"Gendron","year":"2002","journal-title":"Brain Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1007\/s12026-017-8966-3","article-title":"\u03b22-adrenergic stimulation of dendritic cells favors IL-10 secretion by CD4+ T cells","volume":"65","author":"Herv\u00e9","year":"2017","journal-title":"Immunol. Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.physbeh.2010.05.018","article-title":"Psychological stress during exercise: Lymphocyte subset redistribution in firefighters","volume":"101","author":"Huang","year":"2010","journal-title":"Physiol. Behav."},{"key":"B17","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/nm.2399","article-title":"The immunology of stroke: From mechanisms to translation","volume":"17","author":"Iadecola","year":"2011","journal-title":"Nat. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1093\/bja\/71.3.447","article-title":"Actions of the hypnotic anaesthetic, dexmedetomidine, on noradrenaline release and cell firing in rat locus coeruleus slices","volume":"71","author":"Jorm","year":"1993","journal-title":"Br. J. Anaesth."},{"key":"B19","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s12871-020-01025-7","article-title":"Intraoperative dexmedetomidine attenuates norepinephrine levels in patients undergoing transsphenoidal surgery: A randomized, placebo-controlled trial","volume":"20","author":"Kang","year":"2020","journal-title":"BMC Anesthesiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.neulet.2017.04.011","article-title":"Dexmedetomidine confers neuroprotection against transient global cerebral ischemia\/reperfusion injury in rats by inhibiting inflammation through inactivation of the TLR-4\/NF-\u03baB pathway","volume":"649","author":"Kim","year":"2017","journal-title":"Neurosci. Lett."},{"key":"B21","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1212\/WNL.0b013e31822dc795","article-title":"Factors influencing in-hospital mortality and morbidity in patients treated on a stroke unit","volume":"77","author":"Koennecke","year":"2011","journal-title":"Neurology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1161\/01.str.31.6.1223","article-title":"Medical complications after stroke: A multicenter study","volume":"31","author":"Langhorne","year":"2000","journal-title":"Stroke"},{"key":"B23","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s12974-019-1506-4","article-title":"Augmented \u03b22-adrenergic signaling dampens the neuroinflammatory response following ischemic stroke and increases stroke size","volume":"16","author":"Lechtenberg","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3048","DOI":"10.1161\/STROKEAHA.114.006092","article-title":"Follistatin-like 1 attenuates apoptosis via disco-interacting protein 2 homolog A\/Akt pathway after middle cerebral artery occlusion in rats","volume":"45","author":"Liang","year":"2014","journal-title":"Stroke"},{"key":"B25","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.intimp.2016.04.003","article-title":"Dexmedetomidine attenuates inflammatory reaction in the lung tissues of septic mice by activating cholinergic anti-inflammatory pathway","volume":"35","author":"Liu","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s13105-012-0196-5","article-title":"Influence of exercise on NA- and Hsp72-induced release of IFN \u03b3 by the peritoneal suspension of macrophages and lymphocytes from genetically obese Zucker rats","volume":"69","author":"Mart\u00edn-Cordero","year":"2013","journal-title":"J. Physiol. Biochem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1046\/j.1474-8673.2003.00280.x","article-title":"Autonomic innervation of immune organs and neuroimmune modulation","volume":"23","author":"Mignini","year":"2003","journal-title":"Auton. Autacoid Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1161\/01.str.12.2.200","article-title":"Plasma norepinephrine in stroke","volume":"12","author":"Myers","year":"1981","journal-title":"Stroke"},{"key":"B29","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1097\/00000542-200302000-00024","article-title":"The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects","volume":"98","author":"Nelson","year":"2003","journal-title":"Anesthesiology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.imlet.2010.10.001","article-title":"Effects of restraint stress on NALT structure and nasal IgA levels","volume":"135","author":"Oros-Pantoja","year":"2011","journal-title":"Immunol. Lett."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2607","DOI":"10.1161\/01.STR.0000240409.68739.2b","article-title":"Stroke propagates bacterial aspiration to pneumonia in a model of cerebral ischemia","volume":"37","author":"Prass","year":"2006","journal-title":"Stroke"},{"key":"B32","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1023\/a:1024942132705","article-title":"Pulmonary edema and pleural effusion in norepinephrine-stimulated rats-hemodynamic or inflammatory effect?","volume":"250","author":"Rassler","year":"2003","journal-title":"Mol. Cell Biochem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1212\/wnl.57.5.833","article-title":"Prognostic relevance of pathological sympathetic activation after acute thromboembolic stroke","volume":"57","author":"Sander","year":"2001","journal-title":"Neurology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2318","DOI":"10.1161\/STROKEAHA.107.510362","article-title":"Variables associated with 7-day, 30-day, and 1-year fatality after ischemic stroke","volume":"39","author":"Saposnik","year":"2008","journal-title":"Stroke"},{"key":"B35","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.expneurol.2005.08.004","article-title":"Predominant phagocytic activity of resident microglia over hematogenous macrophages following transient focal cerebral ischemia: An investigation using green fluorescent protein transgenic bone marrow chimeric mice","volume":"196","author":"Schilling","year":"2005","journal-title":"Exp. Neurol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1007\/s11481-012-9406-8","article-title":"A transient decrease in spleen size following stroke corresponds to splenocyte release into systemic circulation","volume":"7","author":"Seifert","year":"2012","journal-title":"J. Neuroimmune Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.bja.2019.07.027","article-title":"Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: Systematic review and meta-analysis","volume":"123","author":"Wang","year":"2019","journal-title":"Br. J. Anaesth."},{"key":"B38","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1159\/000065512","article-title":"Complications following acute ischemic stroke","volume":"48","author":"Weimar","year":"2002","journal-title":"Eur. Neurol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s12974-014-0213-4","article-title":"Cross-talk between the inflammatory response, sympathetic activation and pulmonary infection in the ischemic stroke","volume":"11","author":"Winklewski","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"B40","doi-asserted-by":"publisher","first-page":"562154","DOI":"10.1155\/2013\/562154","article-title":"Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4\/NF-\u03baB pathway","volume":"2013","author":"Wu","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"B41","doi-asserted-by":"publisher","first-page":"295","DOI":"10.2147\/JIR.S344521","article-title":"Clenbuterol, a selective \u03b22-adrenergic receptor agonist, inhibits or limits post-stroke pneumonia, but increases infarct volume in MCAO mice","volume":"15","author":"Xu","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1038\/s41589-020-0492-2","article-title":"Activation of the \u03b1 2B adrenoceptor by the sedative sympatholytic dexmedetomidine","volume":"16","author":"Yuan","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s12192-012-0380-0","article-title":"Stress-induced effects, which inhibit host defenses, alter leukocyte trafficking","volume":"18","author":"Zieziulewicz","year":"2013","journal-title":"Cell Stress Chaperones"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1203646\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T10:04:06Z","timestamp":1690970646000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1203646\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,2]]},"references-count":43,"alternative-id":["10.3389\/fphar.2023.1203646"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1203646","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,2]]},"article-number":"1203646"}}