The loss of physical activity after a spinal cord injury results in musculoskeletal deterioration and metabolic dysfunction. Rehabilitation often overlooks the importance of physical activity in the paralyzed limbs for systemic metabolic health. There is a need for safe, feasible exercise interventions to increase physical activity levels in the paralyzed limbs of people with chronic paralysis that have severe musculoskeletal loss. The goal of this work is to 1) develop a gene expression signature after a single dose and long term training using a high force exercise in people with an acute spinal cord injury; 2) develop a novel low force exercise intervention using electrical muscle stimulation to limit force production and increase routine physical activity for chronically paralyzed human skeletal muscle; 3) determine the gene expression signature after a single dose of this novel low force exercise in people with long term paralysis; 4) develop a dose estimate of this low force exercise needed to initiate a phenotype transformation of chronically paralyzed skeletal muscle.
The major findings of this research are 1) a single dose of high force exercise increases the expression of key regulatory genes needed for the transformation of paralyzed skeletal muscle observed after long term training; 2) our novel low force exercise intervention challenges chronically paralyzed muscle but not non-paralyzed muscle; 3) a single dose of low force exercise increases the expression of key regulatory genes needed to improve skeletal muscle health; 4) a dose of at least 4 days per week of our low force exercise is needed to initiate a phenotype transformation of chronically paralyzed skeletal muscle. Together, this work supports the use of a low force exercise intervention for people with long term spinal cord injury and establish the need for future work assessing effects of our low force exercise on the systemic health and quality of life of people with long term spinal cord injury.