Human ventromesencephalic grafts restore dopamine release and clearance in hemiparkinsonian rats

We and others reported previously that transplantation of fetal ventromesencephalic homograft restores the apomorphine-induced rotational behavior 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 was limited to the graft area even 4 months after transplantation. In the present experiments, we transplanted human fetal ventromesencephalic tissue to the 6-OHDA-lesioned rats. After transplantation, rats received chronic cyclosporin and vibramycin treatment. We found that human fetal grafts from the substantia nigra can restore the effects of DA depletion in 6-OHDA-lesioned rats; these fetal grafts were found to reduce the apomorphine-induced rotational behavior and restore K(+)-evoked DA release as well as DA clearance in the striatum. The area with active DA release is far beyond the transplantation site, unlike that seen 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 complete restoration of function than those that received homografts.