Dopaminergic neurons associate with blood vessels in neural transplants

Neural transplantation is an attractive strategy for diseases that result in focal neurodegeneration such as Parkinson's disease, where there is a selective loss of dopaminergic neurons in the substantia nigra of the midbrain. A major drawback to its application, however, is the poor survival of donor dopaminergic neurons. While neurons probably depend on host-derived substances delivered by either diffusion or the establishment of functional vascular connections, the relative importance of each delivery mechanism is not known. We investigated the topography of transplants of embryonic mesencephalic tissue and describe the spatial relationships between transplanted dopaminergic neurons, the host brain, and in-growing blood vessels. Results indicate that transplant vascularization shares features with developmental patterns of brain vascularization. Moreover, the topographical distribution of dopaminergic neurons reflected their proximity to the host brain as well as their distance from vascular elements. Zonal analysis revealed that the majority of dopaminergic neurons were found at or near the host-transplant interface at 1 week after transplantation. Nearest neighbor analysis demonstrated a descending exponential gradient of dopaminergic neurons as a function of their distance from vessels at the same time point. These patterns became more marked with time. Results suggest that rates and patterns of vascularization may be important determinants in the long-term survival of dopaminergic neurons.