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CNS Neurosci Ther. 2016 Jun;22(6):497-506. doi: 10.1111/cns.12523. Epub 2016 Feb 22.

Differential Effects of Antiepileptic Drugs on Focal Seizures in the Intrahippocampal Kainate Mouse Model of Mesial Temporal Lobe Epilepsy.

Author information

1
SynapCell SAS, La Tronche, France.
2
INSERM, U836, Grenoble, France.
3
University Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
4
CHU de Grenoble, Hôpital Michallon, Grenoble, France.

Abstract

AIMS:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

Animal model; EEG; Fast Fourier transform; Focal paroxysmal discharge; Hippocampus; Quantitative EEG

PMID:
26899987
PMCID:
PMC6492802
DOI:
10.1111/cns.12523
[Indexed for MEDLINE]
Free PMC Article

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