HUMAN VENTROMESENCEPHALIC GRAFTS RESTORE DOPAMINE RELEASE AND CLEARANCE IN HEMIPARKINSONIAN RATS

We and others reported previously that transplantation of fetal ventro mesencephalic homograft restores the apomorphine-induced rotational be havior and electrochemical indices of dopamine (DA) depletion in the 6 -hydroxydopamine (6-OHDA)-lesioned rat. We found that regeneration of KCl-evoked DA release and tyrosine hydroxylase (TH) immunoreactivity w as limited to the graft area even 4 months after transplantation. In t he present experiments, we transplanted human fetal ventromesencephali c tissue to the 6-OHDA-lesioned rats. After transplantation, rats rece ived chronic cyclosporin and vibramycin treatment. We found that human fetal grafts from the substantia nigra can restore the effects of DA depletion in B-OHDA-lesioned rats; these fetal grafts were found to re duce the apomorphine-induced rotational behavior and restore K+-evoked DA release as well as DA clearance in the striatum. The area with act ive DA release is far beyond the transplantation site, unlike that see n in the homografted rats. These electrochemical responses correspond to the extended outgrowth of TH-positive neuronal fibers distal to the graft area, Taken together, our data suggest that rats that received human mesencephalic graft had much greater DA innervation and more com plete restoration of function than those that received homografts. (C) 1995 Academic Press, Inc.