Dystrophic changes in mdx muscle regenerating from denervation and devascularization

Abstract

The regenerative capacity of young mdx muscle after a denervating and devascularizing injury (DD) was examined in extensor digitorum longus (EDL) and compared with that of age-matched control mouse EDL. DD of the right EDL was produced at the age approximating the onset of dystrophy in the mdx model, and mice recovered for 2 weeks. Contralateral unoperated EDLs from mdx and control mice served as internal controls for histopathology, myofiber cross-sectional area (CSA), and ultrastructure of fiber regeneration in DD-EDL. Mdx DD-EDL were composed of small, uniformly mature myofibers with mostly peripheral nuclei. This contrasted with control DD-EDL in which fibers were centrally nucleated. In addition, the unoperated mdx EDL exhibited the central nucleation of spontaneous recovery from dystrophy. The CSA distribution of mdx DD-EDL myofibers was significantly shifted toward smaller CSA compared with unoperated mdx EDL, although mean CSA did not differ between the two mdx muscle groups. The CSA distribution of control DD-EDL was significantly different and shifted toward smaller CSA from both unoperated control EDL and from mdx DD-EDL distributions. Ultrastructural features of dystrophy were present in both mdx DD-EDL and in the unoperated mdx EDL, although they appeared more prevalent in the latter. These results suggest that short-term plasticity of mdx muscle recovery from imposed injury may be greater than that of normal muscle in establishing a regenerating fiber population.