{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:19:00Z","timestamp":1790731140697,"version":"4.1.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["T.M. 4248778651"],"award-info":[{"award-number":["T.M. 4248778651"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["428778375"],"award-info":[{"award-number":["428778375"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Schilling Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple consensus statements have called for preclinical randomized controlled trials to improve translation in stroke research. We investigated the efficacy of an interleukin-17A neutralizing antibody in a multi-centre preclinical randomized controlled trial using a murine ischaemia reperfusion stroke model. Twelve-week-old male C57BL\/6 mice were subjected to 45\u2005min of transient middle cerebral artery occlusion in four centres. Mice were randomly assigned (1:1) to receive either an anti-interleukin-17A (500\u2005\u00b5g) or isotype antibody (500\u2005\u00b5g) intravenously 1 h after reperfusion. The primary endpoint was infarct volume measured by magnetic resonance imaging three days after transient middle cerebral artery occlusion. Secondary analysis included mortality, neurological score, neutrophil infiltration and the impact of the gut microbiome on treatment effects. Out of 136 mice, 109 mice were included in the analysis of the primary endpoint. Mixed model analysis revealed that interleukin-17A neutralization significantly reduced infarct sizes (anti-interleukin-17A: 61.77 \u00b1 31.04\u2005mm3; IgG control: 75.66 \u00b1 34.79\u2005mm3; P = 0.01). Secondary outcome measures showed a decrease in mortality (hazard ratio = 3.43, 95% confidence interval = 1.157\u201310.18; P = 0.04) and neutrophil invasion into ischaemic cortices (anti-interleukin-17A: 7222 \u00b1 6108 cells; IgG control: 28 153 \u00b1 23 206 cells; P &amp;lt; 0.01). There was no difference in Bederson score. The analysis of the gut microbiome showed significant heterogeneity between centres (R = 0.78, P &amp;lt; 0.001, n = 40). Taken together, neutralization of interleukin-17A in a therapeutic time window resulted in a significant reduction of infarct sizes and mortality compared with isotype control. It suggests interleukin-17A neutralization as a potential therapeutic target in stroke.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad090","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T11:28:18Z","timestamp":1679570898000},"source":"Crossref","is-referenced-by-count":13,"title":["A preclinical randomized controlled multi-centre trial of anti-interleukin-17A treatment for acute ischaemic stroke"],"prefix":"10.1093","volume":"5","author":[{"given":"Mathias","family":"Gelderblom","sequence":"first","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Kolja","family":"Strecker","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University of M\u00fcnster , 48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5131-2595","authenticated-orcid":false,"given":"Carina","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark , 5000 Odense , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3832-0037","authenticated-orcid":false,"given":"Lidia","family":"Garcia-Bonilla","sequence":"additional","affiliation":[{"name":"Feil Family Brain and Mind Research Institute, Weill Cornell Medicine , New York, NY 10065 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ludewig","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines Sophie","family":"Sch\u00e4dlich","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Piepke","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoline","family":"Degenhardt","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Bernreuther","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Pinnschmidt","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiruma V","family":"Arumugam","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy & Microbiology School of Life Sciences, La Trobe University , Melbourne 3086 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4785-1449","authenticated-orcid":false,"given":"G\u00f6tz","family":"Thomalla","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-7710","authenticated-orcid":false,"given":"Cornelius","family":"Faber","sequence":"additional","affiliation":[{"name":"Translational Research Imaging Center, Clinic of Radiology, University of M\u00fcnster , 48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sedlacik","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Centre for the Developing Brain, School of Biomedical Engineering & Imaging Sciences, King's College London , London WC2R 2LS , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gerloff","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Minnerup","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University of M\u00fcnster , 48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina H","family":"Clausen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark , 5000 Odense , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Anrather","sequence":"additional","affiliation":[{"name":"Feil Family Brain and Mind Research Institute, Weill Cornell Medicine , New York, NY 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