Highly selective SGLT2 inhibitor dapagliflozin reduces seizure activity in pentylenetetrazol-induced murine model of epilepsy

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dc.authoridErdogan, Mumin Alper/0000-0003-0048-444X
dc.authoridErdogan, Arife/0000-0003-2488-2012
dc.authoridsolmaz, volkan/0000-0002-9045-2347
dc.authoridErbas, Oytun/0000-0001-5427-8428
dc.authorwosidErdogan, Mumin Alper/AAR-3140-2021
dc.authorwosidERBAS, OYTUN/ABA-7380-2021
dc.authorwosidErdogan, Arife/GVR-8235-2022
dc.contributor.authorErdogan, Mumin Alper
dc.contributor.authorYusuf, Dimas
dc.contributor.authorChristy, Joanna
dc.contributor.authorSolmaz, Volkan
dc.contributor.authorErdogan, Arife
dc.contributor.authorTaskiran, Emin
dc.contributor.authorErbas, Oytun
dc.date.accessioned2024-06-12T10:59:08Z
dc.date.available2024-06-12T10:59:08Z
dc.date.issued2018
dc.departmentTrakya Üniversitesien_US
dc.description.abstractBackground: Worldwide, over 10 million individuals suffer from drug-resistant epilepsy. New therapeutic strategies are needed to address this debilitating disease. Inhibition of sodium-glucose linked transporters (SGLTs), which are variably expressed in the brain, has been demonstrated to reduce seizure activity in murine models of epilepsy. Here we investigated the effects of dapagliflozin, a highly competitive SGLT2 inhibitor currently used as a drug for diabetes mellitus, on seizure activity in rats with pentylenetetrazol (PTZ) induced seizures. Methods: Laboratory rats (n = 48) were evenly randomized into two experiments, each with four study arms: (1) a vehicle-treated (placebo) arm infused with saline; (2) a control arm infused with PTZ; (3) a treatment arm with PTZ and dapagliflozin at 75 mg/kg, and (4) another treatment arm with PTZ and dapagliflozin at 150 mg/kg. Study subjects were assessed for seizures either via EEG as measured by spike wave percentage (SWP), or clinically via Racine's scales scores (RSS) and time to first myoclonic jerk (TFMJ). Results: Rats treated with dapagliflozin had lower mean SWP on EEG (20.4% versus 75.3% for untreated rats). Behaviorally, treatment with dapagliflozin improved means RSS (2.33 versus 5.5) and mean TFMJ (68.3 versus 196. 7 s). All of these findings were statistically significant with p-values of < 0.0001. There was a trend towards even better seizure control with the higher dose of dapagliflozin at 150 mg/kg, however this was not consistently statistically significant. Conclusions: Dapagliflozin decreased seizure activity in rats with PTZ-induced seizures. This may be explained by the anti-seizure effects of decreased glucose availability and a reduction in sodium transport across neuronal membranes which can confer a stabilizing effect against excitability and unwanted depolarization. The potential clinical role of dapagliflozin and other SGLT2 inhibitors as anti-seizure medications should be further explored.en_US
dc.identifier.doi10.1186/s12883-018-1086-4
dc.identifier.issn1471-2377
dc.identifier.pmid29879920en_US
dc.identifier.scopus2-s2.0-85048295508en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1186/s12883-018-1086-4
dc.identifier.urihttps://hdl.handle.net/20.500.14551/20333
dc.identifier.volume18en_US
dc.identifier.wosWOS:000435006400001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherBiomed Central Ltden_US
dc.relation.ispartofBmc Neurologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectDapagliflozinen_US
dc.subjectEpilepsyen_US
dc.subjectPentylenetetrazolen_US
dc.subjectSodium-Glucose Linked Transporteren_US
dc.subjectSodium-Glucose Transporteren_US
dc.subjectRat-Brainen_US
dc.subjectFunctional Expressionen_US
dc.subjectIschemiaen_US
dc.subjectCotransportersen_US
dc.subjectDamageen_US
dc.subjectSleepen_US
dc.titleHighly selective SGLT2 inhibitor dapagliflozin reduces seizure activity in pentylenetetrazol-induced murine model of epilepsyen_US
dc.typeArticleen_US

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