Growth and functional efficacy of intrastriatal nigral transplants depend on the extent of nigrostriatal degeneration

Previous studies have shown that the functional efficacy of intrastriatal t ransplants of fetal dopamine (DA) neurons in the rat Parkinson model depend s on their ability to establish a new functional innervation of the denerva ted striatum. Here we report that the survival, growth, and function of the grafted DA neurons greatly depend on the severity of the lesion of the hos t nigrostriatal system. Fiber outgrowth, and to a lesser extent also cell s urvival, were significantly reduced in animals in which part of the intrins ic DA system was left intact. Moreover, graft-induced functional recovery, as assessed in the stepping, paw-use, and apomorphine rotation tests, was o btained only in severely lesioned animals, i.e., in rats with >70% DA dener vation of the host striatum. Functional recovery seen in these animals in w hich the 6-hydroxydopamine (6-OHDA) lesion was confined to the striatum was more pronounced than that previously obtained in rats with complete lesion s of the mesencephalic DA system, indicating that spared portions of the ho st DA system, particularly those innervating nonstriatal forebrain areas, m ay be necessary for the grafts to exert their optimal functional effect. Th ese data have implications for the optimal use of fetal nigral transplants in Parkinson patients in different stages of the disease.