Journal article

Disease-modifying effects of a novel T-type calcium channel antagonist, Z944, in a model of temporal lobe epilepsy

Pablo M Casillas-Espinosa, Sandy R Shultz, Emma L Braine, Nigel C Jones, Terrance P Snutch, Kim L Powell, Terence J O'Brien

Progress in Neurobiology | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2019

Abstract

We evaluated whether pharmacologically targeting T-type Ca2+ channels with Z944, a potent and selective antagonist, has disease-modifying effects in a model of temporal lobe epilepsy (TLE) that exhibits spontaneous recurrent seizures, and manifests behavioral and cognitive comorbidities commonly experienced by patients with this condition. Wistar rats underwent implantation of EEG electrodes and one week later 4 h of kainic acid-induced status epilepticus (SE). Animals were randomly assigned to one of 5 different groups: post-SE + Z944 (60 mg/kg/day, n = 8); post-SE + levetiracetam (200 mg/kg/day, n = 9); post-SE + vehicle (n = 8); sham + vehicle (n = 6) or sham + Z944 (60 mg/kg/day, n = 6)...

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Grants

Awarded by NHMRC


Awarded by University of Melbourne Early Career Research Grant


Awarded by NHMRC Career Development Fellowship


Awarded by Canadian Institutes of Health Research


Funding Acknowledgements

The funding for this study was supported by a NHMRC Program Grant to TOB (#APP1091593), a NHMRC Project Grant to TOB (#568729) and NHMRC Project Grant to TOB and KLP (#APP1082215). PMCE was funded by the Melbourne University Graduate Scholarship and the University of Melbourne Early Career Research Grant (#603834). SRS was funded by an NHMRC Career Development Fellowship (#APP1087172). TPS is supported by grants from the Canadian Institutes of Health Research (#10677) the Koerner Foundation and is the Canada Research Chair in Biotechnology and Genomics-Neurobiology.