Neurotoxicity of diphenylhydantoin (DPH) in the cerebellum of Mongolian gerbils--an enzyme histochemical study.

The influence of DPH on the cortex cerebelli of Mongolian gerbils was studied by cytochemical means in acute and chronic experiments. Liver specimens were investigated for comparative purposes. In the cellular elements of the cortex, such as Purkinje cells, neuroepithelial cells, and granule cells, DPH led to an activation of lysosome-bound enzymes and to a decrease of thiamine pyrophosphatase activity in Purkinje cells. Amino-peptidase A, occurring in the entire capillary network, was inhibited by DPH in vivo as well as in vitro. In the liver, however, no change of aminopeptidase A activity could be seen. Enzyme activity of aminopeptidase M and y-glutamyltranspeptidase in cerebellar vessels remained unaffected. Activity of y-glutamyltranspeptidase in the glia, however, increase considerably under the influence of DPH. While in the liver comparable enzymatic changes were most obvious in acute experiments, DPH induce the most distinct changes in the cerebellar cortex during chronic application. The neurotoxic effect of DPH on the cerebellum may on the one hand be due to lesions of the blood-brain barrier, probably only in the cerebellum, and on the other hand to the cerebellum specific relation between GABA metabolism and y-glutamyltranspeptidase activity.