This Proposal is for a continuation of the Clinical Research Center for Acute Spinal Cord Injuries at New York University. The underlying theme of this Center proposal is to study intensively experimental spinal cord injury at a basic pathophysiologic level as a model for clinical spinal cord injury. Major emphasis will be placed on studying the effects of trauma to the spinal cord beyond the acute period following the injury. Changes in the distribution of ions such as calcium, sodium and potassium within the cord, neurophysiologic studies of ascending and descending pathways, and the role of cellular inflammatory response as a cause of progressive damage to the spinal cord in the weeks following the trauma will be used to test the hypothesis that the injury to the spinal cord is progressive beyond the first 12-24 hours. This will provide important information about treatment regimens which may have to be utilized for extended periods if any recovery is to be achieved. In addition to determining these pathophysiologic changes in the spinal cord, the effect of different treatment modalities on these parameters will be tested. The clinical studies will examine the efficacy of opioid antagonists and corticosteroids in the amelioration of spinal cord injury as part of a multi-center randomized trial. Alternate therapies will also be tested in pilot studies. Experimental treatment will test the hypothesis that the opioid receptors play a role in spinal cord injury and that this therapy and corticosteroids are effective even when administered more than 1 hour after injury. The evaluation of therapy on the recovery of injured animals will include neurologic, physiologic and morphologic outcome parameters. This will provide a comprehensive picture of the experimentally injured spinal cord and the response to therapy that will provide a rational basis for selecting clinical therapies. The goal of a Center for Spinal Cord Injury will be realized by the close integration of the component projects of this proposal.
