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Sensorimotor and cognitive dysfunctions post\u2010IS were assessed using neurological function scoring, the rotarod test, the adhesive removal test, the foot\u2010fault test, and the Morris water maze (MWM) test. Brain injury was evaluated by TTC staining, immunofluorescence staining, and Western blotting. For mechanistic exploration, RNA transcriptome sequencing analysis, immunofluorescence staining, and ELISA were employed to determine UA's effects on oxidative stress and neuroinflammation following IS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>UA treatment was confirmed to exert neuroprotective effects against ischemic stroke, as it can inhibit neuronal injury and improve sensorimotor and cognitive functions in rats. Mechanistically, UA upregulates the expression of Nrf2\/HO\u20101, thereby enhancing antioxidant capacity characterized by increased levels of antioxidant enzymes (SOD, GSH, GSH\u2010Px) and decreased level of the lipid peroxidation marker MDA. Additionally, UA suppresses neuroinflammation, which is manifested by reduced levels of pro\u2010inflammatory cytokines (TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20106) and elevated level of the anti\u2010inflammatory cytokine IL\u201010. RNA transcriptome sequencing analysis further revealed that these neuroprotective effects of UA may be associated with inhibition of pathological NF\u2010\u03baB activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Urolithin A may exert neuroprotective effects against ischemic stroke by inhibiting oxidative stress and neuroinflammation. Collectively, this study provides theoretical support for the clinical translation of UA as a poststroke neuroprotective agent.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71081","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:55:33Z","timestamp":1786596933000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Urolithin A Exerts Neuroprotective Effects Against Ischemic Stroke by Inhibiting Oxidative Stress and Neuroinflammation"],"prefix":"10.1002","volume":"32","author":[{"given":"Yanxin","family":"Shao","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Tai'an Shandong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Feng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital Shandong 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