AUTHOR=Aydin Birnur , Ocalan Esmerce Busra , Cakir Aysen , Tuncak Sueda , Koc Cansu , Cansev Mehmet , Alkan Tulin 

TITLE=Uridine treatment protects against blood–brain barrier disruption in a rat model of Li-pilocarpine-induced status epilepticus

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1635247

DOI=10.3389/fnins.2025.1635247

ISSN=1662-453X

ABSTRACT=IntroductionBlood–brain 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.MethodsStatus epilepticus was induced by lithium and pilocarpine administration in male Sprague–Dawley rats which were post-treated with intraperitoneal injection of saline or uridine (500 mg/kg b.w.; twice a day) for 2 days. Blood–brain 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 α1-syntrophin in hippocampal tissue 48 h after SE. Additionally, BBB permeability was determined by measuring brain edema and serum S100B levels.ResultsThe data showed that uridine significantly prevented the reduction in ZO-1 and α1-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.DiscussionTogether, 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.