Intrastriatal cerebellar grafts: differentiation of cerebellar anlage and sprouting of Purkinje cell axons

Abstract

Pieces of cerebellar primordia were obtained from G16 (day 16 of gestation) rat fetuses and stereotaxically injected into the striatum of adult Wistar rats. The transplants were allowed to integrate with the host brain for 2 h up to 6 months after implantation. Ninety four out of 105 transplants perfectly integrated with the host brain (90%) and established the typical trilaminar histoarchitecture of cerebellar cortex. The transplants were sufficiently vascularized. Vessels seen within the grafts provided all ultrastructural elements of a blood-brain barrier. Light microscopic evaluation of graft development showed no considerable retardation of cerebellar histogenesis. Electron microscopic examination disclosed normal ultrastructure of cerebellar neurons, as well as elements of regular synaptic organization. The topic of different graft-to-host projections was investigated 2.5 months after transplantation using the monoclonal Purkinje cell marker anti-Leu-4 (CD3). This method allowed us to detect immunoreactive, morphologically intact axons of grafted Purkinje cells running over long distances (at least 500 μm) within the host striatum. Whilst afferent but in no case efferent connections of heterotopic cerebellar transplants had been demonstrated elsewhere, we could now prove the reciprocal modus of graft-host interaction with heterotopic cerebellar grafts.