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

Publication date: Available online 13 August 2019Source: Progress in NeurobiologyAuthor(s): Pablo M. Casillas-Espinosa, Sandy R. Shultz, Emma L. Braine, Nigel C. Jones, Terrance P. Snutch, Kim L. Powell, Terence J. O’BrienAbstractWe 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 hours 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). Treatments were delivered by continuous subcutaneous infusion for four weeks during which time continuous video-EEG was acquired. Four weeks after completion of treatment, the animals had two further weeks of continuous video-EEG monitoring to evaluate the effects of the different treatments. Behavioral tests were performed to evaluate anxiety, depression, and cognition. On the video-EEG recordings four-week post-treatment, the Z944 group manifest reduced number of seizures (0.01 ± 0.01seizures/day) compa...
Source: Progress in Neurobiology - Category: Neuroscience Source Type: research