We have previously demonstrated that intranigral transplantation of fetal VM tissue and nigrostriatal administration of glial cell line- derived neurotrophic factor (GDNF) regenerate the nigrostriatal dopaminergic pathway and restores striatal dopamine release in hemiparkinsonian rats. It has been found that GDNF mRNA and other TGFb trophic factors are highly expressed in the fetal, but not adult, kidney. The purpose of this study was to examine if fetal kidney tissue could be used as a bridging substrate to restore the nigrostriatal pathway in 6-OHDA lesioned animals. Adult Sprague-Dawley rats were anesthetized and unilaterally injected with 6-OHDA into the medial forebrain bundle. Completeness of the lesion was evaluated by measuring amphetamine-induced rotation. One month after 6-OHDA lesioning. Fetal VM tissues were grafted into the lesioned nigral area followed by transplantation of fetal kidney tissue along a pathway from nigra to striatum. Animals receiving these transplants showed significant decrease in amphetamine-induced rotation one to three months after grafting. Immunocytochemical studies indicated TH (+) fiber tracts grew into the lesioned striatum. Control animals grafted with fetal VM and adult kidney tissue showed no alterations in amphetamine-induced turning. These results indicate that combinations of fetal nigral and kidney transplants may restore the nigrostriatal DA pathway in Parkinsonian rats. As fetal kidney contains a variety of trophic proteins, it may provide a synergistic mixture to optimally promote DA fiber outgrowth. - Parkinsons Disease, Transplantation, Trophic Factors
