{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:52:31Z","timestamp":1779925951608,"version":"3.53.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Blood\u2013brain barrier (BBB) disruption is one of the most striking changes triggered by status epilepticus, which deserves specific attention in terms of novel treatment approaches targeting epileptogenesis. Uridine is a pyrimidine nucleoside with neuroprotective, antiepileptic and antiepileptogenic effects; however, its mechanism of action is not fully characterized. In this study, we aimed to investigate the short-term outcomes of uridine treatment on status epilepticus-induced-BBB dysfunction in an animal model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Status epilepticus was induced by lithium and pilocarpine administration in male Sprague\u2013Dawley rats which were post-treated with intraperitoneal injection of saline or uridine (500\u202fmg\/kg b.w.; twice a day) for 2\u202fdays. Blood\u2013brain barrier structural integrity was assessed by measuring expressions of endothelial tight junction proteins zonula occludens-1 (ZO-1) and occludin, matrix metalloproteinases (MMP-2 and MMP-9), aquaporin-4 (AQP4) water channel and its anchoring protein \u03b11-syntrophin in hippocampal tissue 48\u202fh after SE. Additionally, BBB permeability was determined by measuring brain edema and serum S100B levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The data showed that uridine significantly prevented the reduction in ZO-1 and \u03b11-syntrophin protein levels and attenuated serum S100B levels, indicating protective effects on BBB integrity and AQP4 polarization. In contrast, uridine enhanced brain water content in SE-induced rats, a finding that might be a result of maintained AQP4 polarization and enhanced cytotoxic edema.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Together, our results showed for the first time that post-seizure treatment with uridine provides protection against BBB disruption in an experimental SE model; nevertheless, the long-term effects of this treatment warrant further investigation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2025.1635247","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T04:10:38Z","timestamp":1755576638000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Uridine treatment protects against blood\u2013brain barrier disruption in a rat model of Li-pilocarpine-induced status epilepticus"],"prefix":"10.3389","volume":"19","author":[{"given":"Birnur","family":"Aydin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Busra","family":"Ocalan Esmerce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysen","family":"Cakir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sueda","family":"Tuncak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cansu","family":"Koc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Cansev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tulin","family":"Alkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood-brain barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. 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