Dopaminergic Transplants in Patients with Parkinson's Disease: Neuroanatomical Correlates of Clinical Recovery

For the past 15 years, patients with Parkinson's disease have participated in clinical trials evaluating the efficacy of intrastriatal dopamine transplants. Principally, two donor tissues have been employed, the chromaffin cells of the adrenal medulla and fetal ventral mesencephalon. The clinical response following each type of transplant has been variable. In general, the magnitude and the duration of the clinical response is greater with fetal dopaminergic neurons than with adrenal medullary grafts. Postmortem studies of patients receiving adrenal medullary grafts or fetal nigral implants provide a neuroanatomical framework for the clinical response. Adrenal grafts survive poorly following implantation into the striatum, but they are capable of inducing sprouting of host-derived fibers within the caudate nucleus. In contrast, robust survival of fetal nigral implants can be achieved within the human brain which can provide extensive reinnervation to the parkinsonian striatum. These findings are strikingly similar to what has been seen in rodent and nonhuman primate models of PD. This paper describes the neuroanatomical correlates of dopamine brain grafting in humans and elucidates the pattern of changes seen in dopaminergic systems which are associated with clinical benefit.