INBRE

Previous studies on spinal cord injury (SCI) from our labs have shown that 1) passive exercise training in adult spinal cord transected rats led to a maintenance of muscle mass (i.e. prevented muscle atrophy after SCI), 2) such exercise training restored habituation of the H-reflex (i.e. decreased hyperreflexia), and 3) epidural stimulation in acutely transected animals was able to induce treadmill stepping (an effect which led to the granting of a patent for a method and device for stimulating the spinal cord to induce locomotion). In addition, recent clinical application of this technology was found to promote locomotion for as long as 1000 ft with the aid of only a walker in an incomplete SCI patient (classified quadriplegic, who could stand but not walk). During the past summer, under an AR BRIN Faculty Summer Fellowship, we tested successfully the possibility of combining 1) exercise training, 2) oral L-dopa therapy and 3) epidural stimulation to promote locomotion in transected adult rats. Preliminary data indicate that this combination of therapies may prove efficacious in the restoration of stepping following complete spinal transection in the rat. Studies have continued at the applicant’s home institution under an AR BRIN Academic Year Award (spring 2003 semester). The proposed research is designed to complete the project, which involved investigating the ability of three novel interventions: Bicycle Exercise Training Therapy (BETT), epidural spinal cord stimulation (ESCS), and oral L-dopa, to restore locomotion following SCI. Data will be generated using an established model of SCI in the rat. These studies will provide essential information regarding the optimal combination of pharmacological intervention, exercise duration, and electrical stimulation parameters of the spinal cord necessary to maximize recovery of spinal locomotion following SCI. There is great potential for such information to translate into improved rehabilitation strategies for the human patient with SCI. An indirect benefit of these therapies may be the reduction of hyperreflexia, and presumably spasticity, in some patients with SCI (with concomitant reduction in baclofen therapy). Briefly, the experimental paradigm described below will test the effects of no treatment, each treatment by itself, any two treatments and the combination of all three treatments. The variable to be measured is electromyographic (EMG) activity in the hindlimbs, with analysis of muscle burst timing and amplitude, and step cycle frequency and duration, induced following each form of treatment or combined therapy. The proposed research will generate pilot data in multiple important areas while simultaneously developing multiple innovative technologies that may produce significant breakthroughs in the area of treatment for SCI.

Data generated from these studies to date have allowed Dr. Reese to 1) apply for an NIH R21 grant (scheduled for review this spring) and 2) participate as a co-investigator on the COBRE application submitted from UAMS in January. Funding of this project will allow Dr. Reese to complete this series of investigations without the interruption of teaching and committee responsibilities so that, should the R21 and/or COBRE grants be funded, Dr. Reese can engage in the expansions of this project as described in the aforementioned applications. It should be noted that the COBRE application would not take effect before the end of the summer fellowship, and if the R21 application was funded, unused BRIN funds would be returned. An additional advantage of the BRIN fellowship would be the availability of funding for generating additional data should only one, or neither of the NIH applications is funded. Reviews from both applications will be available this summer, allowing Dr. Reese to respond to critique(s).

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Updated 10/31/2005

The Arkansas INBRE is Supported by a grant from the National Institutes of Health
and the National Center for Research Resources (P20 RR-16460).

Please contact Caroline Miller Robinson regarding questions or comments about this site or our program. For more information about the University of Arkansas for Medical Sciences visit http://www.uams.edu.