The critical period of Purkinje cell degeneration and cerebellar hypoplasia due to bilirubin.

The critical period of Purkinje cell degeneration and cerebellar hypoplasia due to bilirubin was examined in rats with transient hyperbilirubinemia induced by a serial subcutaneous injection of novobiocin from 1 to 3, 5 to 7, 10 to 13, or 16 to 20 days after birth. Animals showing total plasma bilirubin levels of 5 to 7 mg/100 ml 6 h after the final injection were used for this study. In nearly midsagittal sections of the culmen, the percentage of the affected Purkinje cells was 0.9%, 17.1%, 0% and 0% at days 3, 7, 13 and 20, respectively. Thus, the Purkinje cells were most vulnerable to bilirubin between days 5 and 7. Cerebella from the rats which showed transient hyperbilirubinemia at day 3, 7, 13 or 20 were weighed at day 30. The cerebellar weight was significantly low only in rats showing hyperbilirubinemia at day 7. Thus, the critical period of the cerebellar hypoplasia due to bilirubin coincided with the period when the Purkinje cells were most sensitive to bilirubin. These results suggest that the Purkinje cell damage leads to the cerebellar hypoplasia in hyperbilirubinemia.