In accordance with the National Institute of Neurological Disorders and Stroke (NINDS) priorities, the goal of this proposal is to develop a system to discover drugs that have the potential to reduce scarring after spinal cord injury. In the United States, approximately 10,000 new cases of traumatic spinal cord injury occur each year. The cost of care for these patients is estimated to exceed $9 billion per year. Due to the lack of neural regeneration these patients are left with long term sensory and motor disabilities. Neural regeneration is limited by the glial scar that forms following injury. Evidence indicates that chondroitin sulfate (CS) is a component of the scar that inhibits repair. Small molecule inhibitors of CS biosynthesis have the potential to block the formation of the inhibitory scar following an injury. This application proposes to develop a novel high- throughput screening method to discover CS biosynthetic inhibitors. Approximately 10,000 new cases of traumatic spinal cord injury occur each year in the United States. The cost of care for these patients is estimated to exceed $9 billion per year. Neural regeneration is considerably limited by the glial scar that forms following injury. We propose a novel method to discover drug candidates that alter the glial scar in order to promote neural regeneration following spinal cord injury. ? ? ?