Zafirlukast Exacerbates Behavioral Seizure Activity and Blood–Brain Barrier Disruption Despite Modestly Reducing Neuronal Injury Markers in a PTZ‑Induced Early Epileptogenesis Mouse Model

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dc.authorid0000-0003-4026-2972
dc.authorid0000-0002-4530-701X
dc.authorid0000-0002-3155-0633
dc.authorid0000-0001-6081-2308
dc.authorid0000-0002-0525-9690
dc.authorid0000-0002-3759-6616
dc.authorid0000-0002-6383-6724
dc.authorid0000-0002-5238-9738
dc.authorid0000-0002-7483-0184
dc.authorid0000-0003-4227-1637
dc.contributor.authorGörgülü, Volkan
dc.contributor.authorTomruk, Cansın Şirin
dc.contributor.authorErgün, Pelin
dc.contributor.authorÖzdil, Berrin
dc.contributor.authorSancı, Ebru
dc.contributor.authorBuhur, Aylin
dc.contributor.authorSözmen, Eser Y.
dc.contributor.authorKöse, Timur
dc.contributor.authorYavaşoğlu, Nefise Ülkü Karabay
dc.contributor.authorYavaşoğlu, Altay
dc.date.accessioned2026-08-14T07:41:52Z
dc.date.available2026-08-14T07:41:52Z
dc.date.issued2026
dc.departmentFakülteler, Diş Hekimliği Fakültesi, Temel Bilimler Bölümü
dc.description.abstractEpilepsy is one of the most prevalent neurological disorders worldwide, and approximately 25% of patients remain refractory to pharmacological treatment. Blood–brain barrier (BBB) disruption and reactive gliosis are key mechanisms implicated in early epileptogenesis. This study investigated the effects of zafirlukast, a leukotriene receptor antagonist, on BBB permeability, reactive gliosis, and behavioral seizure activity in a pentylenetetrazol (PTZ)-induced early epileptogenesis model in C57BL/6 mice. Zafirlukast was administered twice daily at a dose of 10 mg/kg. Seizure activity was evaluated by behavioral observation in terms of seizure severity, latency, duration, and frequency. BBB permeability was assessed using the Evans Blue assay, and brain tissues were analyzed by biochemical and immunohistochemical methods. The PTZ + ZAFIR group exhibited more severe seizures, characterized by increased seizure frequency and duration, shorter latency, and a higher kindling rate (80% vs. 27%). BBB permeability was also increased, whereas MMP-9 levels remained, suggesting disruption may be linked to direct mechanical effects of recurrent seizures rather than inflammation. Clues suggest that zafirlukast may exert paradoxical effects on two prominent cell types involved in reactive gliosis. While increased GFAP and TGF-β1 expression may reflect enhanced astrocyte activation, changes in IL-1β and Iba1 expression suggest suppression of microglial activation. Notably, pro-inflammatory and oxidative stress markers remained unchanged despite the increase in seizure severity. The observed reduction in neurodegeneration may be attributable to the suppressive effects of zafirlukast on microglial activation and the subsequent reduction in pro-inflammatory cytokine release. These findings indicate a complex role for leukotriene signaling during early epileptogenesis. Further studies using different doses, vehicles, and experimental models are warranted to clarify the effects of zafirlukast on the mechanisms underlying early epileptogenesis. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2026.
dc.identifier.citationGorgulu, V., Tomruk, C. S., Ergun, P., Ozdil, B., Sanci, E., Buhur, A., Sozmen, E. Y., Kose, T., Yavasoglu, N. U. K., & Yavasoglu, A. (2026). Zafirlukast exacerbates behavioral seizure activity and blood-brain barrier disruption despite modestly reducing neuronal injury markers in a PTZ-induced early epileptogenesis mouse model. Molecular Neurobiology, 63(1), Article 812.
dc.identifier.doi10.1007/s12035-026-06110-5
dc.identifier.issn0893-7648
dc.identifier.issue1
dc.identifier.pmid42557520
dc.identifier.scopus2-s2.0-105046557502
dc.identifier.urihttps://hdl.handle.net/20.500.12941/445
dc.identifier.volume63
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakPubMed
dc.indekslendigikaynakScopus
dc.institutionauthorBuhur, Aylin
dc.institutionauthorid0000-0002-3759-6616
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofMolecular Neurobiology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectZafirlukast
dc.subjectEpilepsy
dc.subjectSeizures
dc.subjectBlood–Brain Barrier
dc.subjectGliosis
dc.subjectAstrocytes
dc.titleZafirlukast Exacerbates Behavioral Seizure Activity and Blood–Brain Barrier Disruption Despite Modestly Reducing Neuronal Injury Markers in a PTZ‑Induced Early Epileptogenesis Mouse Model
dc.typeArticle

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