Longitudinal Changes in Glucose Metabolism of Denervated Muscle after Complete Peripheral Nerve Injury

Electrodiagnostic studies can obtain information 2 or 3 weeks after an acute nerve injury. Previous studies have shown increased glucose metabolism in denervated muscles 1 week after injury using 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) positron emission tomography (PET). Therefore, this study aimed to evaluate the changes in glucose metabolism in denervated muscles using serial monitoring by [F-18]FDG PET scans. Denervation was induced in eight male Sprague-Dawley rats (aged 7 weeks old) weighing 200-250 g. The right legs of the rats were denervated by resecting the sciatic nerve in the thigh after the initial skin incision. Two rats were sacrificed 1 and 10 weeks after denervation. Skeletal muscles (gastrocnemius and tibialis anterior) were excised from both the right and left legs of the rats. Staining with hematoxylin and eosin, glucose transporter (GLUT)-1, GLUT-4, and hexokinase II was undertaken. PET/computed tomography (CT) scans were performed on the six remaining rats a total of five times at 1, 2, 5, 8, and 10 weeks after denervation. Regions of interest were drawn on integrated PET/CT images to measure the degree of [F-18]FDG uptake in the right and left lower leg muscles. Target-to-background ratios (TBRs) were calculated by dividing the FDG uptake of the lower leg muscles by that of the upper leg muscles. The TBRs of the denervated muscles were higher than those of the control muscles at both 1 (6.84 +/- 1.98 vs. 1.18 +/- 0.11, p = 0.009) and 2 (4.10 +/- 2.05 vs. 1.86 +/- 0.73, p = 0.0374) weeks after denervation. After 5 (2.18 +/- 0.78 vs. 1.35 +/- 0.47, p = 0.1489), 8 (1.76 +/- 0.18 vs. 1.69 +/- 0.18, p = 0.5127), and 10 (1.76 +/- 0.52 vs. 1.56 +/- 0.37, p = 0.5637) weeks, the difference in the TBRs between the denervated and controls became non-significant. [F-18]FDG PET can visualize increased glucose metabolism in a denervated muscle early as 1 week after injury. Therefore, PET could be adopted as a noninvasive imaging modality for acute nerve injuries. In addition, [F-18]FDG PET may help to understand the role of the nervous system in the control of peripheral tissues.