Lamotrigine-resistant corneal-kindled mice: A model of pharmacoresistant partial epilepsy for moderate-throughput drug discovery

Epilepsia
Zachery KonevalMelissa L Barker-Haliski

Abstract

Despite numerous treatments for epilepsy, over 30% of patients remain resistant to available antiseizure drugs (ASDs). Thus, there is a strong need for more effective ASDs for these individuals. Early ASD discovery has historically relied on acute in vivo seizure models (maximal electroshock, subcutaneous pentylenetetrazol, 6 Hz), which lack the pathophysiology that defines chronic epilepsy. Etiologically relevant rodent models of pharmacoresistant epilepsy exist (eg, phenytoin (PHT)- and lamotrigine (LTG)-resistant amygdala-kindled rat and focal kainic acid mouse), but these models are resource- and labor-intensive and thus unsuitable for frontline ASD discovery. We adapted the LTG-resistant amygdala-kindled rat protocol to the 60 Hz corneal-kindled mouse (CKM) to develop a medium-throughput model of pharmacoresistant chronic seizures. Male CF-1 mice were administered either vehicle (VEH; 0.5% methylcellulose) or LTG (8.5 mg/kg, ip) 30 minutes prior to each twice-daily corneal stimulation until mice achieved kindling criterion. Prototype ASDs were then evaluated in fully kindled mice. Compounds with specific mechanisms of action of interest to epilepsy (fluoxetine, minocycline, and celecoxib) were also evaluated. LTG did not m...Continue Reading

References

Oct 18, 2000·Seizure : the Journal of the British Epilepsy Association·P Kwan, M J Brodie
Mar 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·Wolfgang Löscher, Heidrun Potschka
Dec 1, 2005·Brain : a Journal of Neurology·Stefan Remy, Heinz Beck
Oct 1, 2008·Neuropharmacology·Carlos Luna-TortósWolfgang Löscher
May 15, 2012·Epilepsy & Behavior : E&B·Doris D WangWilliam L Young
Dec 4, 2012·Epilepsy & Behavior : E&B·Jamie Maguire, Jay A Salpekar
Jun 24, 2015·Cold Spring Harbor Perspectives in Medicine·Melissa Barker-Haliski, H Steve White
Jul 29, 2015·Epilepsia·Charles E Begley, Tracy L Durgin
Dec 18, 2015·Neurology·Orrin DevinskyDaniel Friedman
Mar 6, 2016·Journal of Neuropathology and Experimental Neurology·Jaycie L LoewenKaren S Wilcox
Jul 29, 2016·Epilepsia·Melissa L Barker-HaliskiH Steve White
Mar 18, 2017·Neurochemical Research·Melissa L Barker-HaliskiKaren S Wilcox
Mar 24, 2017·Neurochemical Research·Duveau Venceslas, Roucard Corinne
Jul 22, 2017·Frontiers in Neurology·Fei TangBjörn Bauer

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Citations

Jun 30, 2019·Expert Opinion on Drug Discovery·Melissa Barker-Haliski
Jun 17, 2020·Pharmacological Reviews·Wolfgang LöscherAnnamaria Vezzani
Aug 4, 2019·The Journal of Pharmacology and Experimental Therapeutics·Stacey MeekerMelissa Barker-Haliski
Aug 6, 2019·Epilepsy & Behavior : E&B·Daniel Pérez-PérezLuisa Rocha

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