Experimental studies on cerebellar foliation. II. A morphometric analysis of cerebellar fissuration defects and growth retardation after neonatal treatment with 6‐OHDA in the rat

Abstract

Quantitative analyses were undertaken of the gross morphological changes in cerebellar foliation and fissuration patterns in the rat induced by neonatal treatment with 6‐hydroxydopamine (6‐OHDA). After an intracisternal (IC) injection of 100 μg 6‐OHDA, cerebella were much smaller than those of controls and progressively developed abnormal fissures with age, characterized by a loss of pial coverings and fusion of adjacent external granular layers (EGL). Such deformities were most severe anteriorly with relative sparing of posterior fissures. It was also found that the growth rate of individual folia was reduced differentially with a clear linear relationship between the magnitude of the reduction of folial growth rates and the extent to which adjacent fissures were spared. This relationship implied that the basal lamina fractured when the rate of expansion of folia outstripped the rate of deposition of the lamina.The adverse effects of 6‐OHDA on pial fibroblasts were reduced by concomitant IC injection of 10 μg bovine serum albumin (BSA) which allowed fissures to develop normally although most other cerebellar growth defects were unaltered. These findings thus demonstrated the importance of the pia mater for the establishment of fissures.Folia were diminutive after 6‐OHDA treatment but otherwise surprisingly normal even in areas where pia‐lined fissures were absent. This finding suggests that although foliation and fissuration may be complementary morphogenic entities, the former is the primary event resulting from buckling forces generated by proliferation of EGL cells during ontogeny. Basal lamina investment is dependent on glia limitans/pia mater interaction, which normally keeps pace with folial expansion.