Ozone treatment attenuates neuroinflammation and alters miRNA expression in a rat model of post-traumatic epilepsy

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dc.authorid0000-0002-5263-2793
dc.authorid0000-0001-5226-6730
dc.authorid0000-0002-4234-7155
dc.authorid0000-0002-8073-3487
dc.authorid0000-0003-4190-1553
dc.authorid0000-0001-8250-8227
dc.authorid0000-0003-3706-5193
dc.authorid0000-0003-4351-1719
dc.authorid0000-0002-5027-6756
dc.authorid0000-0002-1003-5544
dc.authorid0000-0002-4192-9268
dc.authorid0000-0003-1798-5478
dc.contributor.authorDemir, Hüseyin
dc.contributor.authorDemirtaş, Cumaali
dc.contributor.authorYıldırım, Hava
dc.contributor.authorDemir, Ecem
dc.contributor.authorKıroğlu Uzun, Sezin
dc.contributor.authorŞevgin, Kübra
dc.contributor.authorBeyaztaş, Hakan
dc.contributor.authorGüler, Eray Metin
dc.contributor.authorHekimoğlu, Gulam
dc.contributor.authorÇoşkunpınar, Ender Mehmet
dc.contributor.authorŞanlıer, Nafiye
dc.contributor.authorYıldırım, Mehmet
dc.date.accessioned2026-04-05T09:08:55Z
dc.date.available2026-04-05T09:08:55Z
dc.date.issued2026
dc.departmentFakülteler, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Beyin ve Sinir Cerrahisi Ana Bilim Dalı
dc.description.abstractThe aim of this study was to investigate the effects of intraperitoneal ozone therapy in a post-traumatic epilepsy (PTE) model. An in vivo PTE model was established in male Sprague–Dawley rats, which were randomised to control (n=8), PTE (n=10), and PTE+Ozone (n=10) groups. 0.7 mg/kg ozone was administered intraperitoneally for 3 consecutive days. Seizure activity was video recorded for 120 min and evaluated for latency, frequency, duration, and severity. Behav ioral assessments of locomotor activity, anxiety, and spatial memory were conducted using open field, elevated plus, and radial arm maze tests on days 4–6 after the first ozone application. Blood and brain tissues were collected for biochemical assays (SUR1, TRPM4, IL-1β, IL-6, TNF-α, TAS, TOS, OSI, thiol–disulfide homeostasis), histological analyses (H&E, Cresyl Violet, and 8-OHdG immunostaining), and qRT-PCR of epilepsy-related miRNAs. Significant differences were observed among the groups for all serum and brain biomarkers (p<0.001). The PTE group showed marked increases in SUR1, TRPM4, IL-1β, IL-6, TNF-α, TOS, OSI, TT, NT, and DIS levels, accompanied by a decrease in TAS. Ozone treatment partially reversed these changes by reducing cytokine and oxidative stress markers, improving thiol–disulfide balance, and restoring TAS levels. Behavioural testing revealed beneficial effects of ozone, including reduced immobil ity, fewer errors in the radial arm maze, and increased open-arm exploration. Although seizure severity, latency, and duration were not significantly altered, seizure frequency showed a decreasing trend (p=0.067). Immunofluorescence for 8-OHdG revealed increased hippocampal oxidative DNA damage in the PTE group, which was attenuated following ozone treatment. Analysis of miRNA expression revealed downregulation in the PTE group, whereas ozone treatment resulted in overall upregulation. There was no statistically significant difference between miRNA expression results and the PTE+Ozone group (p=0.056–0.076). Ozone therapy mitigated oxidative stress and inflammation, improved redox homeostasis, enhanced cognitive and locomotor performance, and reduced hippocampal DNA damage in the PTE model. Furthermore, the observed upregulation of specific miRNAs following ozone treatment highlights a potential molecular mechanism contributing to its neuroprotective effects.
dc.description.sponsorshipOpen access funding provided by the Scientific and Techno logical Research Council of Türkiye (TÜBİTAK). The authors have not disclosed any funding. Bu çalışma, Türkiye Bilim ve Teknolojik Araştırma Konseyi (TÜBİTAK) tarafından sağlanan açık erişim fonuyla desteklenmiştir. Yazarlar herhangi bir fon kaynağı açıklamamıştır.
dc.identifier.citationDemir, H., Demirtaş, C., Yıldırım, H., Demir, E., Kıroğlu Uzun, S., Şevgin, K., Beyaztaş, H., Güler, E. M., Hekimoğlu, G., Çoşkunpınar, E. M., Şanlıer, N., & Yıldırım, M. (2026). Ozone treatment attenuates neuroinflammation and alters miRNA expression in a rat model of post-traumatic epilepsy. Neurochemical Research, 51(2), pp. 1-18. https://doi.org/10.1007/s11064-026-04695-w
dc.identifier.doi10.1007/s11064-026-04695-w
dc.identifier.endpage18
dc.identifier.issn1573-6903
dc.identifier.issn0364-3190
dc.identifier.issue2
dc.identifier.pmidPMID: 41718951
dc.identifier.scopus2-s2.0-105030603776
dc.identifier.scopusqualityQ1
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.1007/s11064-026-04695-w
dc.identifier.urihttps://hdl.handle.net/20.500.13055/1383
dc.identifier.volume51
dc.identifier.wosWOS:001696893300001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorDemir, Hüseyin
dc.institutionauthorid0000-0002-5263-2793
dc.language.isoen
dc.publisherSpringer Nature Link
dc.relation.ispartofNeurochemical Research
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectOzone
dc.subjectPost-Traumatic Epilepsy
dc.subjectDentate Gyrus
dc.subjectHippocampus
dc.subjectmiRNA
dc.titleOzone treatment attenuates neuroinflammation and alters miRNA expression in a rat model of post-traumatic epilepsy
dc.typeArticle
dspace.entity.typePublication

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