A single episode of neonatal seizures alters the cerebellum of immature rats.

Summary Purpose To test whether a single episode of early-life seizures may interfere with the development of the cerebellum. The cerebellum is particularly vulnerable in infants, since it is characterized by an important postnatal histogenesis that leads to the settling of adult circuitry. Methods Seizures were induced in 10-day-old Wistar rats with a single convulsive dose (80 μg/g b.w., s.c.) of pentylentetrazole (PTZ). Immediately after rats were treated with 3 H-thymidine ( 3 HTdR, 2.5 μCi/g b.w, s.c.). Rats were killed 4 h later and paraffin sections of the cerebellar vermis were processed for 3 HTdR autoradiography and immunocytochemistry for 2/3 subunits of AMPA glutamate receptor (GluR2/3), glutamate transporter 1 (GLT1) and calbindin. Results Seizures reduced the proliferation rate of cells in the external germinal layer. Purkinje cells showed increased GluR2/3 immunoreactivity. However, some Purkinje cells were unstained or lost. Increased GLT1 immunoreactivity was present in glial cells surrounding Purkinje cells. Calbindin immunoreaction confirmed that some Purkinje cells were missed. The remaining Purkinje cells showed large spheroids along the course of their axon. Conclusions Data indicate that seizures lead to a loss and alteration of Purkinje cells in the cerebellum of immature rats. Since at 10 days of life Purkinje cells are no more proliferating, the loss of Purkinje cells should be permanent.