An Experimental Study on the Histopathological Influence of Diphenylhydantoin to Rat Brain

Abstract

It is well known that there are frequent appearances of cerebellar ataxia due to diphenylhydantoin (DPH) intoxication and it is true that there are a certain number of papers suggesting organic damages of cerebellum in the case of postmortem examination of epileptic patients. The author has carried out three series of experiments using rat; i. e., an embryo rat experiment, an infantile rat experiment, and a matured rat experiment, each consisting of daily observation of general conditions and postmortem investigations with optical and electron microscopes, particularly regarding to the age-dependency of DPH side effect to the rat brain.
1. The embryo rat has presented no particular disturbance to the develop ment of cerebellum either in the experimental group in which DPH were given subcutaneously to pregnant mother rats or in the other group in which DPH were given orally from the pregnant stage through lactaing stage. In the latter group the electron-microscopic examination showed some dubious findings of cerebellar damage more often than in the control group, while the former group presented almost no change and even if a certain change was provoked by DPH administration it was reversible and quickly recuperated by discontinuation of the medication.
2. DPH was given orally for 80 days in the case of infantil e rat, while it was given intraparitoneally in the case of matured rat for 14 days mainly because the rat would be come atactic, comatous and fatal within a few weeks. In both the groups, there were no evidence of loss of Purkinje cell, which was found in the case of epileptic patient. However, there were a few rats in which dark neuron and spheroid were noticed though the induced changes were relatively mild in general.
3. It must be noted that the matured group presented very earlily the DPH - induced changes when compared with infantile group. The difference could be due to the difference of administration method, the author was convinced for several reasons that the matured rat are more sensitive to DPH medication than embryo and infantile rats. It does not mean the DPH-induced changes were severe in the matured rat.
From the results menitoned above, the present author has concluded as follows:
As to the appearance of severe cerebellar damages in the reported case of epilep tic patient, the duration of DPH administration could be important, but the concurrences of several differenct factors such as the fundamental disorders of epilepsy, the frequent repetitions of convulsive seizure and the possible residues of vascular lesions appear to be decisive, for the time being