The goal of these experiments is to analyze the behavior that develops in rats that receive fetal transplants into the site of a complete midthoracic transection at birth, to develop pharmacological approaches that may improve that behavior, and to determine the responses of cells that are axotomized by the transection. Results from our laboratory demonstrate that rats that receive these transplants develop good overground locomotion, characterized by weight support, balance, and coordination between fore and hindlimbs, which is sufficient to support locomotion even in challenging environments. Since this recovery is likely to be mediated in part by regeneration of descending systems, including the serotonergic raphe-spinal and noradrenergic coeruleo-spinal projections, we propose experiments using selected agents as a way to identify the contribution these identified systems. The effect of thee agents will be determined using motor tests that we have developed that measure contributions of weight support, balance and coordination. The morphological consequences of transections and transplants will be analyzed, using retrograde tracers and in situ hybridization with probes to regeneration associated genes, to identify which systems regenerate into or through he transplants; the cellular and molecular environment at athe transplant site will be assessed using immunocytochemical methods to identify the characteristics of environments that promote growth and integration. We will extend these studies to animals transected and given transplants at later ages, including weanling and adults, to determine the extent to which a developmental limitation may exist on the effectiveness of transplant methods. Since transplants integrate well in adults, quantitative measures should reveal recovery of some functions which may differ from those mediate by transplants into neonatal animals.
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