Abstract
Spinal cord injury (SCI) leads to major reductions in function, independent living, and quality of life. Disuse and paralysis from SCI leads to rapid muscle atrophy, with chronic muscle loss likely playing a role in the development of the secondary metabolic disorders often seen in those with SCI. Muscle disuse is associated with mitochondrial dysfunction. Previous evidence has suggested targeting the mitochondria with the tetrapeptide SS-31 is beneficial for muscle health in preclinical models that lead to mitochondrial dysfunction, such as cast immobilization or burn injury. We gave young male mice a sham (n = 8) or 65 kdyne thoracic contusion SCI with (n = 9) or without (n = 9) daily administration of 5.0 mg/kg SS-31. Hindlimb muscle mass and muscle bundle respiration were measured at 7 days post-SCI and molecular targets were investigated using immunoblotting, RT-qPCR, and metabolomics. SS-31 did not preserve body mass or hindlimb muscle mass 7 days post-SCI. SS-31 had no effect on soleus or plantaris muscle bundle respiration. SCI was associated with elevated levels of protein carbonylation, led to reduced protein expression of activated DRP1 and reductions in markers of mitochondrial fusion. SS-31 administration did result in reduced total DRP1 expression, as well as greater expression of inhibited DRP1. Gene expression of proinflammatory cytokines and their receptors were largely stable across groups, although SS-31 treatment led to greater mRNA expression of IL1B, TNF, and TNFRSF12A. In summation, SS-31 was not an efficacious treatment acutely after a moderate thoracic contusion SCI in young male mice.