Spinal cord injury and its eventual outcome is a product of the cellular and molecular mechanisms of degeneration, growth and regeneration. These processes may be best understood by a combination of studies which examine the acute and chronic mechanisms of degenerative phenomena. In addition, since the capacity to regenerate spinal neurons is limited in the adult spinal cord, an attempt to examine regenerative phenomena during development, when such phenomena are enhanced, is an important part of the proposed research. The specific aspects of these phenomena to be explored include an examination of 1) the biochemical pathophysiology of degeneration and 2) the physiology, biochemistry and anatomical characterization of reorganization of nervous tissue subsequent to nerve trauma. The further development and evaluation of a new injury device is an important step toward the control of injury as an independent variable. Alterations in lipids, membrane integrity and recovery, and the ability to induce changes in the metabolic (P02) or ion (Ca++) microenviornment will be studied to assess the effects of ischemia or impact injury to the spinal cord. Interventions into this pathological process will also be attempted with naloxone to improve tissue oxygenation and spinal hypocalcemia. The degree to which such interventions are successful will also be assessed chronically by behavioral or morphometric analysis. Mechanisms of axolemmal synthesis are to be studied by assessing ganglioside contributions to peripheral nerve trauma. Reorganization and regenerative phenomena will be assessed in the cat and developing frog respectively using HRP histochemistry, intracellular neurophysiological techniques, and electron microscopy. The role of nerves in the regenerative plasticity involved in limb regeneration is also to be assessed. Only by studying acute alterations in spinal pathophysiology and attempting to reverse them chronically can we begin to effect changes in the capacity of the central nervous system to use the inherent mechanisms of regeneration that it had, but may have lost, during development.
