Experimental studies on cerebellar foliation. I. A qualitative morphological analysis of cerebellar fissuration defects after neonatal treatment with 6-OHDA in the rat

Abstract

The present report describes the natural history of defective cerebellar fissuration in the rat after neonatal treatment with 6-hydroxydopamine (6-OHDA). Within 24 hours after an intracisternal (IC) injection of 100 micrograms 6-OHDA cerebellar pial fibroblasts degenerated almost completely and were phagocytosed b macrophages within 2-5 days postinjection (dpi) leaving the cerebellar surface denuded of pia. Bergmann glia end feet at first exhibited morphological signs of gliosis and later formed new sprouts that penetrated the basal lamina and grew into the subarachnoid space covering regenerating pial fibroblasts and also invading ectopic colonies of external granular layer (EGL) cells. Breaches in the basal lamina appeared after the pial fibroblast had been destroyed and were confined to areas where Bergmann glia end feet were absent and where EGL cells were opposed to the basal lamina. EGL cells escaped through these fractures into the subarachnoid space in the fissures, where they proliferated to form large colonies of granule and stellate cells. In those fissures in which EGL ectopia featured, opposing folia fused and fissures were lost. These findings suggest that pial fibroblasts and the basal lamina have an important role in maintaining lobular partition during development of the cerebellum, in establishing cerebellar fissures, and in consolidating Bergmann glia-EGL cell relationships as a prerequisite for orderly migration of EGL cells.