Restitution of bromodeoxyuridine-induced changes in cerebellar development.

Previously, it was shown that bromodeoxyuridine (BrdU) in 2-day-old rats caused hypoplasia of the external cerebellar granular layer. Significant restitution was achieved after removal of BrdU by an increase in the rate and duration of proliferative activity of the EGL cells, but abnormal cerebellar cytoarchitecture remained detectable at 35 days of age due mainly to polarity changes in the regenerated cells. The present report concerns repair of the EGL after giving BrdU to 7-day-old rats i.p. (15 mg/100 g body weight) twice daily for 3 days and killed at 15 days-of-age. Now, the regenerative capacity of the EGL was severely curtailed. The proliferative activity of the EGL of the treated animals was similar to normal controls and there was no change in the orientation of either the EGL cells or the parallel fibers. The only noticeable differences were a decrease in the width of the molecular layer and the presence of unusually elongated primary dendrites in many Purkinje cells of the BrdU treated rats. It was concluded that lengthening of the cell cycle time had slowed down the removal of BrdU and thus reduced the regenerative potential of the EGL at this age.