Long-term effects of cografts of pretransected peripheral nerve with adrenal medulla in animal models of Parkinson's disease.

Trophic factor supplementation has been reported to enhance the survivability of grafted adrenal chromaffin cells. Because the content of nerve growth factor in the distal stump of a pretransected peripheral nerve increases markedly 1 day after transection, we injected cografts of adrenal medulla with pretransected peripheral nerve into the striata of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and performed follow-up histological and neurochemical analyses over a 12-month period. Adrenal medullary chromaffin cells cografted with pretransected peripheral nerve survived better than in adrenal grafts alone at 1, 3, and 12 months after transplantation. Host dopaminergic fiber recovery adjacent to the grafts was more prominent in mice with cografts than in mice with adrenal grafts alone at 1 and 3 months after transplantation. Twelve months after transplantation, however, there was no significant difference between the two groups of animals because of the natural recovery of intrinsic dopaminergic fibers from MPTP toxicity. Dopamine concentration in the striata of cografted mice was higher than in mice with adrenal grafts alone at 1 month after transplantation. At 3 and 12 months after transplantation, the natural recovery of dopamine concentration from MPTP toxicity was apparent in both groups of animals and no significant difference was observed between the groups. We conclude that adrenal medullary chromaffin cells can survive for at least 12 months after grafting when cografted with pretransected peripheral nerve. Cografts enhanced the recovery of the host nigrostriatal dopaminergic system up to 3 months after transplantation, but this enhancement was not apparent at 12 months because of the natural recovery of dopaminergic fibers from MPTP toxicity.