Multimodal assessment of nervous and immune system responses following sciatic nerve injury

Subsequent to peripheral nerve compression and irritation, pathophysiological processes take place within nervous and immune systems. Here, we utilized a multimodal approach to comprehend peripheral and central soft tissue changes as well as alterations occurring in systemic analytes following unilateral chronic constriction injury (CCI) of the sciatic nerve in rodents. Using magnetic resonance imaging and [18F]-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography, we demonstrated robust structural abnormalities and enhanced FDG uptake within the injured nerve and surrounding muscle, respectively. To assess whether central morphological changes were induced by nerve injury, diffusion tenor imaging was performed. A decrease in fractional anisotropy in primary motor cortex contralateral to the injury site was observed. Evaluation of a panel of circulating cytokines, chemokines, and growth factors showed decreased levels of interleukin-1β and Fractalkine in CCI animals. Area under the receiver operating curve (ROC) calculations of analyte levels, imaging, and behavioral end points ranged from 0.786 to 1, where behavioral and peripheral imaging end points (eg, FDG uptake in muscle) were observed to have the highest discriminatory capabilities (maximum area under ROC = 1) between nerve injury and sham conditions. Lastly, performance of correlation analysis involving all analyte, behavioral, and imaging data provided an understanding of the overall association amongst these end points, and importantly, a distinction in correlation patterns was observed between CCI and sham conditions. These findings demonstrate the multidimensional pathophysiology of sciatic nerve injury and how a combined analyte, behavioral, and imaging assessment can be implemented to probe this complexity.