Perivascular external granule cells in hereditary cerebellar vermis defect rat: pathogenesis of cerebellar cortical dysplasia.

Hereditary cerebellar vermis defect rats (CVD), a new neurological mutant, developed disorganized cerebellar cortical tissues. The postnatal development of the cerebellum in the CVD was examined histologically and immunohistochemically. A main pathological change in the CVD was abnormal perivascular cell aggregations, beginning to be observed from postnatal day 5. Around postnatal day 14, perivascular cells increased in number and many of them showed vigorous bromodeoxyuridine incorporation activities, as seen in the normal external granule cells (EGCs). The perivascular cells and EGCs were strongly positive for low affinity nerve growth factor receptor. These immunohistochemical results revealed that abnormal perivascular cells were heterotopic EGCs. The perivascular cells led to dysplastic abnormalities of lamination and abnormal cell positioning in the CVD. These findings indicate that abnormal perivascular aggregations of EGCs play an important role in the pathogenesis for cerebellar cortical dysplasia of CVD.