Cell culture neurotoxicity assays

Several measurements require the collection of nervous tissue at necropsy and homogenization of the tissues prior to analysis simple tissue procedures and associated measurements often do not indicate the localization of effects. Assays using tissue microdissection and in vitro cell cultures can help in the understanding of neurotoxic mechanisms, and these are being used more widely (Abdulla and Campbell 1992 Costa 1998 Harry et al. 1998). The development of assays such as neural gold protein, amyloid precursor protein, neuron specific enolase, heat shock proteins, and amyloid precursor proteins to study nervous diseases may find applications in some toxicology studies where the assays can be adapted for laboratory animals (de la Monte et al. 1997 Fitzpatrick et al. 2000 Rajdev and Sharp 2000). 

In an attempt to find an in vitro assay to predict differences in the neurotoxic potential of bisindole alkaloids, an assay using cultured rat midbrain cells was developed. This system provided a qualitative measure of the effect of compounds on neuronal tissue, and when several compounds (for which clinical toxicity data were available) were evaluated using this method the results were consistent in rank order with the compounds clinical manifestation of neurotoxicity. When vinepidine was studied in this system, it was found to produce a minimal effect (Fig. 7). 

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