{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:51:05Z","timestamp":1790171465154,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,2,5]],"date-time":"2022-02-05T00:00:00Z","timestamp":1644019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008061","name":"Fundaci\u00f3n Mutua Madrile\u00f1a","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inflammasomes are cytosolic multiprotein complexes which, upon assembly, activate the maturation and secretion of the inflammatory cytokines IL\u20101\u03b2 and IL\u201018. However, participation of the NLRP3 inflammasome in ischaemic stroke remains controversial. Our aims were to determine the role of NLRP3 in brain ischaemia, and explore the mechanism involved in the potential protective effect of the neurovascular unit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>WT and NLRP3 knock\u2010out mice were subjected to ischaemia by middle cerebral artery occlusion (60\u2009min) with or without treatment with MCC950 at different time points post\u2010stroke. Brain injury was measured histologically with 2,3,5\u2010triphenyltetrazolium chloride (TTC) staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a time\u2010dependent dual effect of NLRP3. While neither the pre\u2010treatment with MCC950 nor the genetic approach (NLRP3 KO) proved to be neuroprotective, post\u2010reperfusion treatment with MCC950 significantly reduced the infarct volume in a dose\u2010dependent manner. Importantly, MCC950 improved the neuro\u2010motor function and reduced the expression of different pro\u2010inflammatory cytokines (IL\u20101\u03b2 and TNF\u2010\u03b1), NLRP3 inflammasome components (NLRP3 and pro\u2010caspase\u20101), protease expression (MMP9), and endothelial adhesion molecules (ICAM and VCAM). We observed a marked protection of the blood\u2013brain barrier (BBB), which was also reflected in the recovery of the tight junction proteins (ZO\u20101 and Claudin\u20105). Additionally, MCC950 produced a reduction of the CCL2 chemokine in blood serum and in brain tissue, which lead to a reduction in the immune cell infiltration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that post\u2010reperfusion NLRP3 inhibition may be an effective acute therapy for protecting the blood\u2013brain barrier in cerebral ischaemia with potential clinical translation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15732","type":"journal-article","created":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T11:04:14Z","timestamp":1636801454000},"page":"1395-1410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Time\u2010dependent dual effect of NLRP3 inflammasome in brain ischaemia"],"prefix":"10.1111","volume":"179","author":[{"given":"Alejandra","family":"Palomino\u2010Antolin","sequence":"first","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina Instituto de Investigaci\u00f3n Sanitaria\u2010Hospital Universitario de la Princesa  Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando, Departamento de Farmacolog\u00eda y Terap\u00e9utica, Facultad de Medicina UAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Narros\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina Instituto de Investigaci\u00f3n Sanitaria\u2010Hospital Universitario de la Princesa  Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando, Departamento de Farmacolog\u00eda y Terap\u00e9utica, Facultad de Medicina UAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Farr\u00e9\u2010Alins","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina Instituto de Investigaci\u00f3n Sanitaria\u2010Hospital Universitario de la Princesa  Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando, Departamento de Farmacolog\u00eda y Terap\u00e9utica, Facultad de Medicina UAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Sevilla\u2010Montero","sequence":"additional","affiliation":[{"name":"Instituto de Investigacion Sanitaria Princesa (IIS\u2010IP), Department of Medicine, School of Medicine Universidad Autonoma of Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Decouty\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina Instituto de Investigaci\u00f3n Sanitaria\u2010Hospital Universitario de la Princesa  Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando, Departamento de Farmacolog\u00eda y Terap\u00e9utica, Facultad de Medicina UAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Belen","family":"Lopez\u2010Rodriguez","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina Instituto de Investigaci\u00f3n Sanitaria\u2010Hospital Universitario de la Princesa  Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando, Departamento de Farmacolog\u00eda y Terap\u00e9utica, Facultad de Medicina UAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Fluorescence Imaging Group, Departamento de Fisiolog\u00eda, Facultad de Medicina Universidad Aut\u00f3noma de Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7688-7531","authenticated-orcid":false,"given":"Luis","family":"Monge","sequence":"additional","affiliation":[{"name":"Fluorescence Imaging Group, Departamento de Fisiolog\u00eda, Facultad de Medicina Universidad Aut\u00f3noma de Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana I.","family":"Casas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Personalised Medicine, MHeNs Maastricht University  Maastricht The Netherlands"},{"name":"Department of Neurology University Clinics Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Calzada","sequence":"additional","affiliation":[{"name":"Instituto de Investigacion Sanitaria Princesa (IIS\u2010IP), Department of Medicine, School of Medicine Universidad Autonoma of Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4704-3019","authenticated-orcid":false,"given":"Javier","family":"Egea","sequence":"additional","affiliation":[{"name":"Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina Instituto de Investigaci\u00f3n Sanitaria\u2010Hospital Universitario de la Princesa  Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando, Departamento de Farmacolog\u00eda y Terap\u00e9utica, Facultad de Medicina UAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,5]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"S4157","article-title":"The concise guide to pharmacology 2021\/22: Ion channels","volume":"178","author":"Alexander S. P. H.","year":"2021","journal-title":"British Journal of Pharmacology"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.17.6.1304"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.17.3.472"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-15-05528.2001"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30177-6"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-132"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-016-0343-2"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.2.127"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419090112"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/676489"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-011-0469-0"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60584-5"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2005.07.004"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1703"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1941874415578532"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2017.12.009"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18030496"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13812-z"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.11.004"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.2.4"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2399"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2017.09.006"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133328"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3452"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.023620"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527311312030012"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701366104"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00018"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14703"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1381-0"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000248"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1418-07.2007"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10523"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201810248"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.1.227"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.26.4.676"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.242"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1459-1"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15732","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.15732","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15732","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T10:58:04Z","timestamp":1693133884000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.15732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,5]]},"references-count":42,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1111\/bph.15732"],"URL":"https:\/\/doi.org\/10.1111\/bph.15732","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.22541\/au.160943650.03302626\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.1101\/2020.10.08.332007","asserted-by":"object"}]},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,5]]},"assertion":[{"value":"2020-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}