Questions arising from recent clinical neural transplantation trials in Parkinson's disease have under-scored the necessity for a thorough experimental evaluation of the structural and functional consequences of this procedure. The present study investigated the neuroanatomical host reaction to intrastriatal implants in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydro-pyridine (MPTP)-treated nonhuman primates. Nine monkeys (Cebus apella) received intrastriatal implants using either a stereotactic approach with a silver tissue carrier or an open microsurgical procedure. Seven of these animals received intrastriatal adrenal medullary autografts, while two received control implants consisting of the tissue carrier alone. One month following transplantation, the hosts' brains were evaluated via immunohistochemical and routine histologic methods. In both MPTP-treated and normal monkeys, enhanced ipsilateral expression of tyrosine hydroxylase-like immunoreactive (TH-IR) fibers in the caudate nucleus was observed, despite minimal survival of adrenal chromaffin cells in the implants. The intensity of this response was greatest adjacent to the implant site, but a clearly increased degree of ipsilateral striatal fiber staining also could be seen several millimeters from the graft. TH-IR fibers also were more dense and of thicker caliber throughout the nigrostriatal and mesolimbic pathways ipsilateral to the implant. Control stereotactic implants, consisting of a silver tissue carrier alone, produced a similar enhancement of immunoreactive fibers, suggesting an induction of TH-IR fibers by the parenchymal injury produced during surgical implantation. There are two major hypotheses proposed to explain why adrenal medullary grafts may promote functional recovery in human parkinsonism: (1) replacement of lost striatal neurotransmitter (dopamine) by the viable grafted tissue, or (2) induction of recovery of remaining host dopaminergic systems by the implantation procedure. Our current data appear to support the latter.
ASJC Scopus subject areas
- Developmental Neuroscience