Phenytoin neurotoxicity in developing mouse cerebellum in tissue culture

Phenytoin applied to developing neonatal mouse cerebellar cultures at concentrations of 9-46 micrograms/ml of nutrient medium from the day of explantation to 16 days in vitro induced cerebellar cortical degeneration. The degree of neurotoxicity correlated with drug concentration. Purkinje cells were the most susceptible of the cerebellar elements, and intracerebellar nucleus neurons were the most resistant. In contrast, mature mouse cerebellar explants were resistant to chronic exposure to high concentrations of phenytoin.