Evaluation of metformin effects in the chronic phase of spontaneous seizures in pilocarpine model of temporal lobe epilepsy

Mehrabi, S. and Sanadgol, N. and Barati, M. and Shahbazi, A. and Vahabzadeh, G. and Barzroudi, M. and Seifi, M. and Gholipourmalekabadi, M. and Golab, F. (2018) Evaluation of metformin effects in the chronic phase of spontaneous seizures in pilocarpine model of temporal lobe epilepsy. Metabolic Brain Disease, 33 (1). pp. 107-114.

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Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the �ketogenic diet�. Here we have investigated the effects of metformin in the rat pilocaroin model of TLE. Male rats were treated with intra peritoneal injection of pilocarpine hydrochloride, in dose of 360 mg/kg to induce status epilepticus (SE). At 45 day after induction of SE, metformin was injected intraperitoneally in dose of 250 mg/kg/day for 5 days. We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB). We have shown that this reduced expression pattern is mediated by the transcriptional co-repressor CtBP (C-terminal binding protein). Moreover, metformin decreased mechanistic target of rapamycin (mTOR) activation through activation of AMP-activated protein kinase (AMPK) signaling pathway. Our findings have been shown that metformin has anticonvulsant and antiepileptic properties, and suggesting that antiglycolytic compounds such as metformin may represent a new class of drugs for treating epilepsy. © 2017, Springer Science+Business Media, LLC.

Item Type: Article
Additional Information: cited By 3
Uncontrolled Keywords: brain derived neurotrophic factor; brain derived neurotrophic factor receptor; carboxy terminal binding protein; hydroxymethylglutaryl coenzyme A reductase kinase; mammalian target of rapamycin; metformin; repressor protein; unclassified drug, adult; AMPK signaling; animal experiment; animal model; animal tissue; anticonvulsant activity; Article; controlled study; drug effect; drug potency; epileptic state; epileptogenesis; evaluation study; immunohistochemistry; immunoreactivity; male; nonhuman; pilocarpine-induced seizure; protein expression; rat; temporal lobe epilepsy
Subjects: WL Nervous System
QV Pharmacology
Depositing User: eprints admin
Date Deposited: 31 Dec 2018 07:10
Last Modified: 24 Aug 2019 04:32
URI: http://eprints.iums.ac.ir/id/eprint/5920

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