EXTRACELLULAR IONIC AND PH REGULATION

The first response of the spinal cord to traumatic insult is a rapid breakdown of ion homeostasis. The resultant ion shifts persist for hours, and have been implicated in several models of cellular injury. The broad objective of this study is to elucidate the mechanisms which initiate and prolong these ionic derangements. Experiments will utilize ion-selective microelectrode techniques to quantity the magnitude and time course of extracellular ion shifts following graced contusion injured of the rat spinal cord. Initial studies will address derangements of extracellular calcium, potassium, sodium, chloride, bicarbonate and pH, with emphasis on the biophysics of ion diffusion in an around the injury site. We will then focus on the acid-base status of the injured spinal cord, to address the role of blood glucose and focal ischemia in the evolution of acute acidosis and secondary injury. Extracellular pH, blood flow and tissue lactate will be measured in hyperglycemic, normoglycemic and hypoglycemic animals, following spinal cord injury. A similar protocol will be utilized in a four week chronic study, to determine the role of these factors in electrophysiologic and histologic outcome. In the final year, the activity-dependent shifts of extracellular pH and volume will be studied in chronic spinal cord injury. These experiments will focus on the role of reactive glial cells in the modulation of extracellular fluid composition around the chronic lesion site. This project will provide the first detailed characterization of extracellular ion dynamics in spinal cord injury. Information obtained will provide important insights into the mechanisms of acute and chronic spinal dysfunction, and will serve to test and amplify current hypotheses of cellular injury.