Cerebral cortical injury due to vascular insufficiency at birth or at maturity is a major cause of chronic disability in the U.S. While afflicted individuals have had little hope of recovery from permanent symptoms, numerous recent experiments involving neuronal transplants suggest the use of fetal grafts in nervous system repair. Our recent findings demonstrate that fetal cortical tissue will survive, grow and form host-transplant interconnections when grafted into lesion cavities made in the newborn neocortex. In order to pursue these results, the proposed experiments represent a multidisciplinary study of neuronal transplants in the reconstruction of the damaged cerebral cortex. Anatomical studies using antero- and retrograde tracing techniques are proposed to further examine the projections of such grafts and to study possible transplant-host interconnections using adult recipients. Since unilateral cortical lesions in the newborn will induce remodelling of the opposite hemisphere, the possible effects of transplants on host plasticity will also be examined. Retrograde tracing studies have demonstrated host thalamo- transplant connections as well as transplant projections to the host spinal cord. Experiments are proposed to examine single-unit responses within grafts to peripheral sensory and thalamic electrical stimulation as well as body movements or heart rate changes evoked by transplant microstimulation. Transplant afferents from cholinergic, noradrenergic and serotonergic cell groups have also been described using retrograde tracing techniques. Immunocytochemical studies are proposed to determine more precisely the origin and distribution of these transplant afferents. Biochemical analyses using HPLC methods are proposed to quantify monoaminergic levels within the grafts. Using several transplant paradigms, further biochemical studies are proposed in search of correlations between transmitter levels and transplant growth. Recent studies demonstrated the use of fetal cortical grafts to promote recovery from cortical lesion-induced deficits on learning tasks. Experiments are proposed to examine the effects of transplants on motor deficits associated with cortical lesions.
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