Staged anticonvulsant screening for chronic epilepsy.

ABSTRACT:

Objective

Current anticonvulsant screening programs are based on seizures evoked in normal animals. One-third of epileptic patients do not respond to the anticonvulsants discovered with these models. We evaluated a tiered program based on chronic epilepsy and spontaneous seizures, with compounds advancing from high-throughput in vitro models to low-throughput in vivo models.

Methods

Epileptogenesis in organotypic hippocampal slice cultures was quantified by lactate production and lactate dehydrogenase release into culture media as rapid assays for seizure-like activity and cell death, respectively. Compounds that reduced these biochemical measures were retested with in vitro electrophysiological confirmation (i.e., second stage). The third stage involved crossover testing in

SUBMITTER: Berdichevsky Y 

PROVIDER: S-EPMC5224819 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature