Evaluation of a Human Neural Stem Cell Culture Method for Prediction of the Neurotoxicity of Anti-epileptics

Abstract

Human neural stem cells have been proposed as an in vitro model to predict neurotoxicity. In this study, the potential of in vitro cultures of human-derived neurospheres to predict the effects of various anti-epileptic drugs (sodium valproate, phenytoin, carbamazepine and phenobarbitone) was evaluated. In general, these drugs had no significant effects on cell viability, total cellular protein, and neuronal process length at low doses, but at high doses these parameters were reduced significantly. Therapeutic doses of sodium valproate and phenytoin had a clear effect on neurosphere size and cell migration, with a significant reduction in both parameters when compared with the control group. The other drugs (carbamazepine and phenobarbitone) reduced neurosphere size and cell migration only at higher doses. The expression levels of glial fibrillary protein and tubulin III, which were used to identify astrocytes and neuronal cells, respectively, were reduced in a dose-dependent manner that became significant at high doses. The levels of glial fibrillary protein did not indicate any occurrence of reactive astrocytosis.