Reduced skeletal muscle perfusion accompanies skeletal muscle atrophy after severe spinal cord injury.

The goal of this study was to gain insight into an understudied physiological mechanism that may influence skeletal muscle atrophy following spinal cord injury (SCI). Specifically, we quantified skeletal muscle blood flow (BF) rates in paralyzed hindlimbs throughout the acute to subacute recovery period in a severe contusion SCI model. Secondary objectives were to characterize temporal changes in circulating and tissue-level markers of capillary density and vascular dysfunction, and vascular-related gene expression within hindlimb skeletal muscle. We hypothesized that SCI would reduce skeletal muscle BF and be accompanied by increases in circulating markers of vascular dysfunction, along with reductions in skeletal muscle capillary density and vascular-related gene expression. Four-month-old Sprague-Dawley male rats underwent T9 laminectomy (sham surgery) or severe contusion SCI. Hindlimb skeletal muscle mass, absolute BF rates, and mass-corrected BF rates were lower at 1, 2, and 4 wk in SCI versus sham, with the most distinct BF differences present in the soleus (∼50% lower, P < 0.001). Bulk RNA sequencing revealed that genes related to coagulation, blood vessel maintenance, and endothelial cell health were lower in soleus muscle after SCI, with most differences occurring at 1-2 wk. Circulating platelet endothelial cell adhesion molecule-1, a marker of vascular dysfunction, was higher at 2-3 wk post-SCI (P < 0.05), whereas no differences in soleus capillary density were detected. Our results reveal reduced limb perfusion and signs of vascular dysfunction in paralyzed hindlimb skeletal muscle during the acute post-SCI period in a rodent severe SCI model. Future studies examining mechanisms of vascular dysfunction after SCI or testing interventions to improve vascular function should consider this timeframe.NEW & NOTEWORTHY First study to assess temporal blood flow/perfusion rates in paralyzed plantar flexor muscles throughout the acute to subacute period after SCI and to determine the relation with skeletal muscle capillarization. Results demonstrate that reduced skeletal muscle perfusion that develops in the paralyzed plantar flexor muscles throughout the acute to subacute post-SCI recovery period may be driven by reduced limb perfusion and damage to endothelial cells within skeletal muscle vasculature, independent of skeletal muscle capillarization.