Physical rehabilitation improves muscle function following volumetric muscle loss injury

BACKGROUND: Given the clinical practice of prescribing physical rehabilitation for the treatment of VML injuries, the present study examined the functional and histomorphological adaptations in the volumetric muscle loss (VML) injured muscle to physical rehabilitation. METHODS: Tibialis anterior muscle VML injury was created in Lewis rats (n = 32), and were randomly assigned to either sedentary (SED) or physical rehabilitation (RUN) group. After 1 week, RUN rats were given unlimited access to voluntary running wheels either 1 or 7 weeks (2 or 8 weeks post-injury). At 2 weeks post-injury, TA muscles were harvested for molecular analyses. At 8 weeks post-injury, the rats underwent in vivo function testing. The explanted tissue was analyzed using histological and immunofluorescence procedures. RESULTS: The primary findings of the study are that physical rehabilitation in the form of voluntary wheel running promotes ~ 17% improvement in maximal isometric torque, and a ~ 13% increase in weight of the injured muscle, but it did so without significant morphological adaptations (e.g., no hypertrophy and hyperplasia). Wheel running up-regulated metabolic genes (SIRT-1, PGC-1α) only in the uninjured muscles, and a greater deposition of fibrous tissue in the defect area of the injured muscle preceded by an up-regulation of pro-fibrotic genes (Collagen I, TGF-β1). Therefore, it is plausible that the wheel running related functional improvements were due to improved force transmission and not muscle regeneration. CONCLUSIONS: This is the first study to demonstrate improvement in functional performance of non-repaired VML injured muscle with physical rehabilitation in the form of voluntary wheel running. This study provides information for the first time on the basic changes in the VML injured muscle with physical rehabilitation, which may aid in the development of appropriate physical rehabilitation regimen(s).