This Program on Spinal Cord Injury represents a bending of interdisciplinary approaches to explore the potential for restoring function in the injured spinal cord. With this long-term objective in mind, various anatomical, behavioral, electrophysiological, neurophysiological, and microsurgical methods will be used to achieve the following immediate goals: (i) to examine the capacity of fetal CNS and peripheral nerve (PNS) grafts to mediate anatomical and functional repair in acute and chronic injuries, (ii) to develop models that will ultimately permit definitive correlative analyses of therapeutic strategies aimed at restoring sensory, motor, and/or autonomic function, (iii) to test new approaches that may permit in-depth studies of behavior and cellular neurophysiology, and (iv) to demonstrate fundamental events underlying functional recovery in the amphibian spinal cord. Accordingly, Project 1 will examine the ability of fetal CNS grafts to establish host- graft synaptic interactions in the chronically injured spinal cord, as well as the capacity of these grafts to prevent the death of certain spinal neurons following cord damage in the adult rodent: methods will also be developed for intraspinal transplantation into the adult cat in conjunction with our Core laboratory. Project 2 focuses on the problem of spasticity, as manifested in the cat, and seeks to establish approaches that will permit direct correlations between non-invasive physiological evaluations and electrophysiological recordings. Project 3 will test the efficacy of PNS grafts in restoring somatosensation and segmental reflex activity in the cat and primate. Project 4 will study the neurophysiology and synaptic organization of the cat sacrocaudal cord - a region which may serve as a novel model for studies of spinal cord plasticity and regeneration. Project 5 will explore sensory physiology and the ascending pathways that subserve cortical perception of respiration in various animal models, as well as in humans with spinal cord injuries. Collectively, these subproject will provide a comprehensive and interactive investigation of various aspects of spinal cord motor, sensory, and autonomic function that are of fundamental scientific and clinical interest.
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