Targeting Mitochondrial Function in Traumatic Spinal Cord Injury

Spinal cord injury (SCI) is a major debilitating event that constitutes a major health issue in the United States and more effective therapies that limit neurological dysfunction are warranted. The pathological events that occur soon after SCI are complex, making it necessary to identify treatment approaches that will promote cell survival at acute times following injury. The studies proposed in this application are based on the central hypothesis that maintaining mitochondrial function is a critical factor for promoting cell survival in SCI. The overall goal of this proposal is to demonstrate that inhibiting injury-induced mitochondrial permeability transition (mPT) will lead to a feasible and effective treatment in SCI. These studies will demonstrate that inhibiting mPT with NIM811, a non-immunosuppressive cyclosporine A (CsA) analog, has therapeutic implications in the treatment of SCI. The goal of this proposal will be addressed by accomplishing the following specific two Specific Aims: 1) determine the optimal dose and delivery time of NIM811 required to improve mitochondrial function following acute SCI, and 2) determine the functional significance of post-injury NIM811 treatment using the optimal dosing paradigm obtained in Aim I. Given the lack of any effective therapeutic strategies, the outcome of these studies will have important implications for the treatment of acute SCI.