{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:43:48Z","timestamp":1791337428929,"version":"4.3.1"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"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":["Annals of Neurology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>No current therapy prevents swelling after ischemic stroke, and pathways leading to edema formation are not completely understood. We have found the immune regulator soluble ST2 (sST2) to be a candidate mediator of edema formation. In the current study, we sought to identify a mechanistic relationship between sST2 and edema in ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a proteomics survey for plasma biomarkers of edema in patients with large ischemic stroke and verified associations with outcome. We performed middle\u2010cerebral artery occlusion (MCAO) in rats and measured sST2 expression. We used both in vitro and in vivo techniques to determine the cellular source of sST2. We generated a sST2 knockout rat line and performed MCAO to determine the effect of knockout on brain edema, endothelial and microglial gene expression, and blood\u2013brain barrier integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found sST2 to be associated with edema, outcome and mortality after large ischemic stroke. We replicated the elevation in plasma sST2 in a rat model of stroke and found brain endothelium as the cell type with highest expression. Knockout of sST2 did not alter lesion volume but was associated with reduced swelling and increased staining for the tight junction protein zona occludens 1 (ZO\u20101).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Plasma sST2 level is associated with edema, functional outcome, and mortality after ischemic stroke. Knockout of sST2 reduced post\u2010stroke cerebral edema and was associated with increased staining for the tight junction protein ZO\u20101. These findings establish a mechanistic link between sST2 and brain edema and highlight its potential as a future therapeutic target. ANN NEUROL 2026;99:134\u2013147<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78006","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:13:31Z","timestamp":1755695611000},"page":"134-147","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Brain Endothelial Soluble\n                    <scp>ST2<\/scp>\n                    Production and Cerebral Edema in a Rat Model of Ischemic Stroke"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0878-8464","authenticated-orcid":false,"given":"Matthew B.","family":"Bevers","sequence":"first","affiliation":[{"name":"Division of Neurocritical Care, Department of Neurology Brigham and Women's Hospital  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"An","sequence":"additional","affiliation":[{"name":"Division of Neurocritical Care, Department of 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