The behavioral, biochemical, and histological effects of tissue implants in rodent and primate models of parkinsonism is being studied. The grafts which have been examined include fetal and adult dopaminergic and nondopaminergic tissues. There is some behavioral improvement with any operative trauma to the caudate, whether a graft is placed or not. Generally, fetal tissue grafts (dopaminergic or nondopaminergic) lead to a much greater degree of recovery than adult tissue grafts or trauma alone. - The histologic observation of dopaminergic fiber ingrowth (sprouting) in all these animals suggests that the improvement is mediated through a neurotrophic interaction. We are trying to determine the cell-to-cell interaction which leads to new growth of fibers from an adult neuron, using in vivo and in vitro methods. Two major areas of emphasis are: what cascade of events in the host after trauma leads to sprouting and why does fetal tissue enhance the recovery (even nondopaminergic tissue). The current experiments include implantation of term amnion into hemiparkinsonian monkeys (solid tissue into preformed cavities), cell suspension implants of term amnion into rats, and biochemical and molecular analysis of the neurotrophic factor(s) produced by amnion cells. We are also incorporating laminin into a slow-release polymer and implanting this in hemiparkinsonian rats. To further investigate the host response to tissue trauma, we are implanting inflammatory cells in the denervated caudate. Macrophages, T-cells, and microglia, alone or combined, and their secretory products such as IL-1 are being studied. We are now using autoradiographic techniques to study the blood brain barrier, receptor binding and dopamine uptake in the inflammatory cell implant model.
