{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T11:43:40Z","timestamp":1786621420963,"version":"build-2736575974"},"reference-count":34,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>Inflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading to poor outcome. Interleukin-1 (IL-1) is an important regulator of post-stroke inflammation, and blocking its actions is beneficial in pre-clinical stroke models and safe in the clinical setting. However, the distinct roles of the two major IL-1 receptor type 1 agonists, IL-1\u03b1 and IL-1\u03b2, and the specific role of IL-1\u03b1 in ischemic stroke remain largely unknown. Here we show that IL-1\u03b1 and IL-1\u03b2 have different spatio-temporal expression profiles in the brain after experimental stroke, with early microglial IL-1\u03b1 expression (4\u2009h) and delayed IL-1\u03b2 expression in infiltrated neutrophils and a small microglial subset (24\u201372\u2009h). We examined for the first time the specific role of microglial-derived IL-1\u03b1 in experimental permanent and transient ischemic stroke through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Microglial IL-1\u03b1 deletion did not influence acute outcome after ischemic stroke. However, microglial IL-1\u03b1 knock out (KO) mice showed reduced peri-infarct vessel density and reactive astrogliosis at 14 days post-stroke, alongside long-term impaired functional recovery. Our study identifies for the first time a critical role for microglial IL-1\u03b1 on post-stroke neurorepair and recovery, highlighting the importance of targeting specific IL-1 mechanisms in brain injury to develop effective therapies.<\/jats:p>","DOI":"10.1177\/0271678x251323371","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T06:11:14Z","timestamp":1742451074000},"page":"1479-1492","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Selective deletion of interleukin-1 alpha in microglia does not modify acute outcome but may regulate neurorepair processes after experimental ischemic stroke"],"prefix":"10.1177","volume":"45","author":[{"given":"Elo\u00efse","family":"Lemarchand","sequence":"first","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health (FBMH), The University of Manchester, Manchester, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester, Northern Care Alliance NHS Foundation Trust, The Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1466-0099","authenticated-orcid":false,"given":"Alba","family":"Grayston","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health (FBMH), The University of Manchester, Manchester, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester, Northern Care Alliance NHS Foundation Trust, The Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health (FBMH), The University of Manchester, Manchester, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester, Northern Care Alliance NHS Foundation Trust, The Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyako","family":"Rogers","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health (FBMH), The University of Manchester, Manchester, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester, Northern Care Alliance NHS Foundation Trust, The Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake","family":"Ouvrier","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Clinical Neuroscience Research Center, Tulane University School of Medicine, Orleans, LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Llewellyn","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health (FBMH), The University of Manchester, Manchester, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester, Northern Care Alliance NHS Foundation Trust, The Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freddie","family":"Webb","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health (FBMH), The University of Manchester, Manchester, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester, Northern Care Alliance NHS Foundation Trust, The Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolett","family":"L\u00e9n\u00e1rt","sequence":"additional","affiliation":[{"name":"\u201cMomentum\u201d Laboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1d\u00e1m","family":"D\u00e9nes","sequence":"additional","affiliation":[{"name":"\u201cMomentum\u201d Laboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brough","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health (FBMH), The University of Manchester, Manchester, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester, Northern Care Alliance NHS Foundation Trust, The Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9646-4456","authenticated-orcid":false,"given":"Stuart M","family":"Allan","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health (FBMH), The University of Manchester, Manchester, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester, Northern Care Alliance NHS Foundation Trust, The Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J","family":"Bix","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Clinical Neuroscience Research Center, Tulane University School of Medicine, Orleans, LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9986-4401","authenticated-orcid":false,"given":"Emmanuel","family":"Pinteaux","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health (FBMH), The University of Manchester, Manchester, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, University of Manchester, Northern Care Alliance NHS Foundation Trust, The Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705462"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.020750"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.11.012"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.010001"},{"key":"e_1_3_6_6_2","first-page":"1043","article-title":"Central and haematopoietic interleukin-1 both contribute to ischaemic brain injury in mice","volume":"6","author":"Denes A","year":"2013","unstructured":"Denes A, Wilkinson F, Bigger B, et\u00a0al. Central and haematopoietic interleukin-1 both contribute to ischaemic brain injury in mice. Dis Model Mech 2013; 6: 1043\u20131048.","journal-title":"Dis Model Mech"},{"key":"e_1_3_6_7_2","first-page":"279","article-title":"Biological activity and brain actions of recombinant rat interleukin-1\u03b1 and interleukin-1\u03b2","volume":"9","author":"Anforth HR","year":"1998","unstructured":"Anforth HR, Bluthe RM, Bristow A, et\u00a0al. Biological activity and brain actions of recombinant rat interleukin-1\u03b1 and interleukin-1\u03b2. Eur Cytokine Netw 1998; 9: 279\u2013288.","journal-title":"Eur Cytokine Netw"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2008.02.015"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-186"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13422"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1599-9"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_3_6_13_2","first-page":"4","article-title":"Fibroblast-specific deletion of IL-1 receptor-1 reduces adverse cardiac remodeling following myocardial infarction","volume":"5","author":"Bageghni SA","year":"2019","unstructured":"Bageghni SA, Hemmings KE, Yuldasheva NY, et\u00a0al. Fibroblast-specific deletion of IL-1 receptor-1 reduces adverse cardiac remodeling following myocardial infarction. JCI Insight 2019; 5: 4.","journal-title":"JCI Insight"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.12.001"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1820168116"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-08-662650"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.10.2136"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5376-06.2007"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0582-9"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1464-20.2020"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-019-00388-3"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24501"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-15-05528.2001"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt287"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.012"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-3357"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.25.9.1794"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000041283.53351.CB"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24359"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109048"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22727"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30442-3"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.06.028"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50901-0"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X251323371","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X251323371","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X251323371","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:15:34Z","timestamp":1777493734000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X251323371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,20]]},"references-count":34,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1177\/0271678X251323371"],"URL":"https:\/\/doi.org\/10.1177\/0271678x251323371","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,20]]}}}