Twenty-first century challenges for in vitro neurotoxicity

Abstract

During the last 40 years, studies incorporating in vitro methodologies have greatly advanced our understanding of human nerve cell biology. Attempts have been made to apply these to investigations of neurotoxicity. Due to the complexity of the nervous system, underpinned by an array of integrated interactions between a host of cell types, it is concluded that, at present, alternative neural models are most successful in determining the underlying mechanisms which can cause perturbation of normal functioning of the nervous system, both in adults and during the embryonic period. The use of tiered batteries of test models has been proposed in screening programmes for neurotoxicity, with the generation of much encouraging data in laboratories across the globe. This review aims to discuss the development of neural alternatives, considers the various model systems available, and highlights specific neuronal endpoints which can be tested, in addition to the cytotoxic evaluation of neuronal viability. Developments in molecular and stem cell biology, which are appropriate to neural tissue, and which offer the prospect of exciting advances for the next decade, are cited.