Abstract
1 The aim of this study was to evaluate the effect of high concentrations of vigabatrin (γ-vinyl GABA) and of GABA on myelin of the central nervous system cultures.
2 Explants of rat cerebellum were cultured for 14-19 days in vitro on collagen-coated coverslips in Leighton tubes. They were exposed for up to 14 days to 500 nmol ml-1 vigabatrin or to 1000 nmol ml-1 GABA.
3 Qualitative and quantitative blind examination of living cultures and of Sudan black B-stained slides showed mild toxicity of both drugs for myelinated fibres. No clear-cut differences could be demonstrated between the two compounds, although vigabatrin seemed slightly more toxic than GABA at these doses.
4 In electron microscopy, no patent intramyelinic oedema nor primary demyelination were seen. On the contrary, some degenerating myelinated fibres and astrocytic gliosis were seen in both experimental conditions. The changes involved axons as well as myelin sheaths.
5 The toxicity of GABA and vigabatrin was surprisingly mild in this very sensitive model.
Keywords: vigabatrin, γ-vinyl GABA, toxicology, GABA, intramyelinic oedema, tissue culture, myelin
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