The overall goal of this project is to demonstrate the ability of the f32-adrenoceptor agonist, albuterol, an FDA approved therapeutic for obstructive respiratory conditions and xirradiation in combination to oppose irreversible loss of locomotor function due to contusion, the most common type of spinal cord injury (SCI). At present, only methyiprednisolone 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 outgrowth of previous work in which J32-agonists or 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 determine (1) the therapeutic window and optimum dose of albuterol for sparing spinal cord tissue and locomotor function following contusion in an established model of SCI developed by the Multicenter Animal Spinal Cord Injury Study (MASCIS) (2) and the efficacy of albuterol and x-irradiation in combination. Optimization of beta2-agonist treatment and x-irradiation of the contused spinal cord may lead to a useful therapeutic modality for SCI.
Use of beta 2-agonists like albuterol alone or together with x-irradiation maybe useful therapies for spinal cord injuries.
| Kim, Haeyoung; Livingston, Dennis M (2006) A high mobility group protein binds to long CAG repeat tracts and establishes their chromatin organization in Saccharomyces cerevisiae. J Biol Chem 281:15735-40 |
