{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T21:16:33Z","timestamp":1786482993187,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The blood\u2013brain barrier (BBB) is a semi\u2010permeable microvascular barrier, composed of endothelial cells conjoined by tight junction proteins. Following pathological conditions, i.e., traumatic brain injury (TBI), BBB dysfunction occurs, leading to microvascular hyperpermeability, resulting in cerebral edema formation and elevated intracranial pressure. Recent evidence suggests that the activation of pro\u2010inflammatory signaling pathways is critical to BBB dysfunction. The NLRP3 inflammasome has been implicated as a key component of pro\u2010inflammatory signaling. The aim of this study was to determine the upstream regulators of NLRP3 inflammasome activation that cause subsequent BBB aberration and microvascular hyperpermeability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Brain microvascular endothelial cells were exposed to benzoyl ATP (BzATP) with or without MCC950. We employed immunocytochemical localization of tight junction proteins, fluorometric enzymatic assays, total gene expression analyses of ZO\u20101, and monolayer permeability studies to assess the effect of BzATP\u2010induced injury on NLRP3 inflammasome activation\/inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BzATP treatment induced monolayer hyperpermeability and increased caspase\u20101 and MMP\u20109 activities. NLRP3 inhibition decreased caspase\u20101 and MMP\u20109 activities and rescued BzATP\u2010induced monolayer permeability significantly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NLRP3 inflammasome signaling is critical to BBB endothelial cell dysfunction. Extracellular ATP is an upstream promoter of BBB hyperpermeability. NLRP3 inflammasome activation leads to subsequent caspase\u20101 and MMP\u20109\u2010mediated tight junction protein disarray.<\/jats:p><\/jats:sec>","DOI":"10.1111\/micc.70006","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:57:35Z","timestamp":1741741055000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Regulation of <scp>BzATP<\/scp>\u2010Induced Blood\u2013Brain Barrier Endothelial Cell Hyperpermeability by <scp>NLRP3<\/scp> Inflammasome Inhibition"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9115-5379","authenticated-orcid":false,"given":"Aliyah","family":"Anderson","sequence":"first","affiliation":[{"name":"Department of Surgery Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O'lisa 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