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In this study, we explore the role and molecular mechanisms of OA\u2010NO\n                    <jats:sub>2<\/jats:sub>\n                    in maintaining blood\u2013brain barrier (BBB) integrity and enhancing neurovascular function during ischemic stroke, with a particular emphasis on the activation of endothelial PPAR\u03b3 signaling pathways. Endothelial cell\u2010selective PPAR\u03b3 conditional knockout (EC\u2010PPAR\u03b3 cKO) and wild\u2010type (WT) mice underwent 1\u2009h middle cerebral artery occlusion (MCAO) with 1\u20137\u2009days of reperfusion. Mice were treated with oleic acid (OA) or OA\u2010NO\n                    <jats:sub>2<\/jats:sub>\n                    (5\u2009mg\/kg) via tail vein 2\u2009h after MCAO. Neurobehavioral deficits were assessed on days 3, 5, and 7 after MCAO. Neuroinflammation and BBB function were assessed on days 1 or 2 after MCAO by immunohistochemistry, RT\u2010qPCR, or Western blot analysis. Compared to OA controls, intravenous administration of OA\u2010NO\n                    <jats:sub>2<\/jats:sub>\n                    led to reduced BBB leakage in ischemic brains, as indicated by a significant decrease in the extravasation of BBB tracers. This reduction in BBB leakage was also almost abolished in the EC\u2010PPAR\u03b3 cKO mice. Furthermore, OA\u2010NO\n                    <jats:sub>2<\/jats:sub>\n                    treatment reduced brain infarction in stroke mice, but this protective effect was completely reversed in the EC\u2010PPAR\u03b3 cKO mice. Interestingly, OA\u2010NO\n                    <jats:sub>2<\/jats:sub>\n                    treatment promoted a shift towards an anti\u2010inflammatory microglial phenotype (M2) in the peri\u2010infarct regions of WT mice, but not in EC\u2010PPAR\u03b3 cKO mice. Mechanistically, OA\u2010NO\n                    <jats:sub>2<\/jats:sub>\n                    increased levels of major endothelial tight junction proteins in WT mice but not in EC\u2010PPAR\u03b3 cKO mice following ischemic stroke. These findings suggest that OA\u2010NO\n                    <jats:sub>2<\/jats:sub>\n                    activation of endothelial PPAR\u03b3 signaling cascade attenuates neurovascular injury after ischemic stroke.\n                  <\/jats:p>","DOI":"10.1111\/bpa.70037","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T07:26:17Z","timestamp":1755933977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nitro\u2010oleic acid activation of endothelial\n                    <scp>PPAR\u03b3<\/scp>\n                    signaling pathway alleviates neurovascular injury and improves functional outcomes in ischemic stroke"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6497-7847","authenticated-orcid":false,"given":"Tianqing","family":"Xiong","sequence":"first","affiliation":[{"name":"Geriatric Research Education and Clinical Center Veterans 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Pennsylvania USA"},{"name":"Department of Neurology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7169-3858","authenticated-orcid":false,"given":"Ke\u2010Jie","family":"Yin","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center Veterans Affairs Pittsburgh Healthcare System  Pittsburgh Pennsylvania USA"},{"name":"Department of Neurology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania 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