High-Low Training to Induce Long-Term Motor and Respiratory Plasticity after SCI

Grants and Contracts Details


Neilson LOI Due May 11, 2020 PI: Ann M. Stowe Collaborators: Warren Alilain & John Gensel Title: High-Low training to induce long-term motor and respiratory plasticity after SCI Abstract: In the United States, there are an estimated 288,000 people with spinal cord injury (SCI), with fewer than 1% of this patient population presenting with complete recovery. Recent clinical studies show that exercise improves motor and cognitive deficits after SCI, but the magnitude of exercise-induced plasticity may be limited in adults because of reductions in growth factor production that occur with aging. Brief intermittent exposures to low oxygen (i.e. hypoxia) have also been shown to promote recovery after SCI and might provide a synergistic therapeutic effect with exercise. In this grant, we propose to develop a synergistic model that couples hypoxic exposures with voluntary exercise to determine the effects of long-term H-L intervention on post-SCI recovery. “High-Low” training (H-L) is a novel strategy that couples repeated hypoxic exposures (i.e. High altitude living) with daily normoxic exercise (i.e. Low altitude training) to improve exercise performance in athletes. Our prior work in an NIH-supported pilot study to determine if H-L reduces cognitive deficits in Alzheimer’s disease (AD) found that H-L is well tolerated in the healthy aged subjects and subjects with mild AD. Five weeks of H-L improved cardiopulmonary fitness and upregulated growth factors in the cerebrospinal fluid. This grant will use a C2 hemisection model of SCI to determine if H-L training improves functional recovery, motor, and respiratory plasticity in mice. Specifically, we hypothesize that H-L training enhances structural and functional plasticity, beyond either exercise or repeated exposures to systemic hypoxia alone, to improve motor recovery and reduce persistent deficits after SCI. At 6 weeks post-SCI, we will initiate 8 weeks of H-L training in 4 mo. old male and female mice, with a second cohort undergoing an additional 4-week post-H-L period. Aim 1 will test the hypothesis that High-Low training improves motor and cognitive recovery and enhances sustained neuronal and vascular plasticity in C2 hemisected animals. Aim 2 will test the hypothesis that High-Low training induces sustained respiratory motor plasticity and cardiopulmonary recovery in C2 hemisected animals. These studies will provide evidence that an already-used clinical intervention shows efficacy in promoting neurorepair after SCI.
Effective start/end date7/31/2110/30/23


  • Craig H. Neilsen Foundation: $300,000.00


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