title: Differential Effects of Antiepileptic Drugs on Focal Seizures in the Intrahippocampal Kainate Mouse Model of Mesial Temporal Lobe Epilepsy.
abstract: Mesial temporal lobe epilepsy (MTLE) is the most common form of drug-refractory epilepsy. Most of the morphological and electrophysiological features of human MTLE can be reproduced in a mouse by a unilateral intrahippocampal injection of kainate (MTLE mouse model). The effects of antiepileptic drugs (AEDs) on the occurrence of recurrent focal hippocampal seizures in this model remain to be specified. Here, we addressed the pharmacological reactivity of this model to the most commonly used AEDs.
  
  
  
  Using depth electroencephalographical (EEG) recordings, we tested the dose-response effects of acute injection of nine AEDs on the occurrence of hippocampal paroxysmal discharges (HPDs) as well as on ictal and interictal power spectra in the MTLE mouse model.
  
  
  
  Valproate, carbamazepine, and lamotrigine dose dependently suppressed HPDs and modified the general behavior and/or EEG activity. Levetiracetam and pregabalin suppressed HPDs at high doses but without any behavioral nor interictal EEG changes. Finally, phenobarbital, tiagabine, vigabatrin, and diazepam suppressed HPDs in a dose-dependent manner at doses devoid of obvious behavioral effects.
  
  
  
  The MTLE mouse model displays a differential sensitivity to AEDs with a greater efficacy of drug that facilitates GABAergic transmission. This model provides an efficient tool to identify new treatment for drug-resistant forms of focal epilepsies.
authors.affiliation: SynapCell SAS, La Tronche, France.
authors.forename: Venceslas
authors.initials: V
authors.lastname: Duveau
authors.affiliation: SynapCell SAS, La Tronche, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Pouyatos
authors.affiliation: SynapCell SAS, La Tronche, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Bressand
authors.affiliation: SynapCell SAS, La Tronche, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Bouyssières
authors.affiliation: INSERM, U836, Grenoble, France.|University Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: Tanguy
authors.initials: T
authors.lastname: Chabrol
authors.affiliation: SynapCell SAS, La Tronche, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Roche
authors.affiliation: INSERM, U836, Grenoble, France.|University Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.|CHU de Grenoble, Hôpital Michallon, Grenoble, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Depaulis
authors.affiliation: SynapCell SAS, La Tronche, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Roucard
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D058256:Brain Waves / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000150:complications*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005583:Fourier Analysis; D006624:Hippocampus / Q000187:drug effects; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid
keywords: Animal model; EEG; Fast Fourier transform; Focal paroxysmal discharge; Hippocampus; Quantitative EEG