The overall goal of this project is to demonstrate the ability of the beta2-adrenoceptor agonist, clenbuterol, and x-irradiation in combination to oppose irreversible loss of locomotor function due to contusion, the most common type of spinal cord injury (SCI). At present, only methylprednisolone has been shown to have efficacy in humans for SCI. However, the extent of recovery is limited so that additional or alternative treatments are needed. Potentially superior countermeasures are available, but require a demonstration of efficacy in an appropriate animal model of spinal cord contusion injury prior to use in patients. The proposed studies are an out growth of previous work in which clenbuterol of x-irradiation enhanced recovery of locomotor function following SCI in rats. Recovery of locomotor function, in turn, correlated with sparing of myelinated white matter at the injury site by these agents. We will examine in detail the ability of clenbuterol and x-irradiation to spare spinal cord tissue and locomotor function following contusion in an established model of SCI developed by the Multicenter Animal Spinal Cord Injury Study (MASCIS). PROPOSED COMMERCIAL APPLICATION: Optimization of beta2-agonist treatment in combination with x-irradiation of the contused spinal cord may lead to a useful therapeutic modality for treatment of SCI.
Thesaurus Terms: drug design /synthesis /production, neuropharmacologic agent, spinal cord injury X ray, chordate locomotion, combination therapy, neuroprotectant laboratory rat
