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ORIGINAL RESEARCH article

Front. Neurosci.

Sec. Translational Neuroscience

Volume 19 - 2025 | doi: 10.3389/fnins.2025.1635247

This article is part of the Research TopicWomen in Translational Neuroscience 2025View all articles

Uridine Treatment Protects Against Blood-Brain Barrier Disruption in a Rat Model of Li-Pilocarpine-Induced Status Epilepticus

Provisionally accepted
Birnur  AydinBirnur Aydin1Bursa  OcalanBursa Ocalan2Aysen  CakirAysen Cakir2Sueda  TuncakSueda Tuncak2Cansu  KocCansu Koc2Mehmet  CansevMehmet Cansev2Tulin  AlkanTulin Alkan2*
  • 1Bursa City Hospital, Bursa, Türkiye
  • 2Bursa Uludag Universitesi Tip Fakultesi, Nilfer, Türkiye

The final, formatted version of the article will be published soon.

Introduction: Blood-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.Sprague-Dawley rats which were post-treated with intraperitoneal injection of saline or uridine (500 mg/kg b.w.; twice a day) for two 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.The data showed that uridine significantly prevented the reduction in ZO-1 and α1syntrophin protein levels and attenuated serum S100B levels, indicating protective effects on BBB integrity and AQP4 polarization. In contrast, uridine enhanced brain water content in SEinduced rats, a finding that might be a result of maintained AQP4 polarization and enhanced cytotoxic edema.Discussion: 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.

Keywords: Status Epilepticus, Uridine, Blood-Brain Barrier, Brain Edema, aquaporin-4

Received: 26 May 2025; Accepted: 28 Jul 2025.

Copyright: © 2025 Aydin, Ocalan, Cakir, Tuncak, Koc, Cansev and Alkan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Tulin Alkan, Bursa Uludag Universitesi Tip Fakultesi, Nilfer, Türkiye

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