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-weeks in SCI vs 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 weeks. Circulating PECAM-1, a marker of vascular dysfunction, was higher 2-3 weeks post-SCI (p<0.05), while 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.