Spinal cord injury and its eventual outcome is clearly a by-product of the complex processes of primary and secondary degeneration and the presumptive attempts of the adult spinal cord to express plastic or regenerative behavior after the original lesion. Our Center has used a combination of approaches to examine and manipulate the acute factors that accompany the degenerative phenomenon. In addition, we have exploited the known capacity of young vertebrates to regenerate spinal pathways with our studies that attempt to relate the plastic behavior of fetal spinal pathways to processes of spinal reorganization and development. It is the working hypothesis of our Center that the factors which contribute to a relative lack of spinal regeneration in adult mammals are expressed in such a way that intrinsic growth potentials are never reached. Individual projects span a wide range of disciplines and methodologies in pursuit of these objectives. Our first two projects (1-2) will use our recently developed electro-mechanical impact device to study acute and chronic responses to impact injury, to characterize the neurochemical sequelae to traumatic injury (Project 1) and investigate the physiological roles that fetal transplants may play in recover processes known to be initiated after injury (Project 2). Adult regenerative phenomena and developmental processes related thereto are studied in other projects. Project 3 examines the normal and altered circuitry of specific somatic and visceral reflexes in the cat spinal cord. The delayed development of descending pathways in the opossum is taken advantage of in the next project (Project 4). Since all brainstem pathways seem to have a critical period during which they express plastic behaviors (growing around induced lesions), this project asks questions about the generality of the phenomenon. Ascending systems seem to show similar plasticity in preliminary data presented by this author. This project therefore provides an excellent model system in which a developing mammal can be studied in vivo. Project 5 should allow the elucidation of certain mechanisms of action of gangliosides at the biochemical and molecular level, particularly as they relate to plastic behavior of the central nervous system and growth phenomena related thereto. This project clearly relates to all of those above it since it addresses basic issues related to the ability of gangliosides to modulate biochemical mechanisms of degeneration such as alterations in protein phosphorylation (Project 1), to clarify the role of gangliosides in neuritogenesis during spinal grafting (Project 2) and explore the roles of such substances in developmental plasticity (Projects 3-4). Utilization of such biochemical approaches will undoubtably amplify the anatomical and physiological information to be gathered in similar animals. Such multifaceted approaches have led to important collaborative research that would have otherwise been unlikely outside of the center concept.
