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Neutrophil \u03b2<jats:sub>1<\/jats:sub> adrenoceptors (\u03b21AR) have been linked to neutrophil migration during exacerbated inflammation. Given the central role of neutrophils in cerebral damage during stroke, we hypothesize that \u03b21AR blockade will improve stroke outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Rats were subjected to middle cerebral artery occlusion\u2013reperfusion to evaluate the effect on stroke of the selective \u03b21AR blocker metoprolol (12.5\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) when injected i.v. 10\u2009min before reperfusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Magnetic resonance imaging and histopathology analysis showed that pre\u2010reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24\u2009h and vasogenic oedema at 7\u00a0days. Metoprolol\u2010treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti\u2010inflammatory phenotype (N2, YM1<jats:sup>+<\/jats:sup>). Additional inflammatory models demonstrated that metoprolol specifically blocked neutrophil migration via \u03b21AR and excluded a significant effect on the glia compartment. Consistently, metoprolol did not protect the brain in neutrophil\u2010depleted rats upon stroke. In patients suffering an ischaemic stroke, \u03b21AR blockade by metoprolol reduced circulating neutrophil\u2013platelet co\u2010aggregates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our findings describe that \u03b21AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15963","type":"journal-article","created":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T04:48:50Z","timestamp":1664599730000},"page":"459-478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Neutrophil \u03b2<sub>1<\/sub> adrenoceptor blockade blunts stroke\u2010associated neuroinflammation"],"prefix":"10.1111","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3236-7822","authenticated-orcid":false,"given":"Agust\u00edn","family":"Clemente\u2010Morag\u00f3n","sequence":"first","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC)  Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV)  Madrid 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