FUNCTIONAL AND ANATOMICAL RECONSTRUCTION OF THE 6-HYDROXYDOPAMINE LESIONED NIGROSTRIATAL SYSTEM OF THE ADULT-RAT

In an attempt to reconstruct the 6-hydroxydopamine lesioned nigrostria tal system of the adult rat we have combined homotopic grafting of emb ryonic ventral mesencephalon suspensions with the implantation of long oblique ''bridge'' grafts of fibroblast growth factor-4-transfected R N-22 schwannoma cells stretching from the site of the neuronal grafts to the striatum. At seven weeks after receiving both grafts, animals w ere killed and processed for immunohistochemistry against tyrosine hyd roxylase. Tyrosine hydroxylase-immunoreactive axons were seen to exten d from the nigral grafts, along the bridge graft to the striatum where terminal arborizations could be seen. The retrograde tracer Fluoro-go ld was injected intrastriatally in some of the experimental animals an d was taken up by grafted neurons confirming their projection to the s triatum. In parallel to the anatomical reconstruction of the system, a decrease in amphetamine-induced rotation was demonstrated in those an imals receiving both grafts which had received > 98% complete lesions. This decrease was greatest in those animals with the most tyrosine hy droxylase-immunoreactive axons in their bridge grafts. The presence of the bridge graft also led to an increase in neuronal graft survival w ith twice as many tyrosine hydroxylase-immunoreactive neurons being fo und in the grafts of those animals that had received both grafts compa red to those that had received a neuronal graft but no bridge graft.