Evidence of induced muscle regeneration persists for years in the mouse

INTRODUCTION: Efficient repositioning of centralized nuclei after injury has long been assumed, with centralized nuclei frequently cited as indicators of ongoing regeneration. However, reports of centralized nuclei that persist after full recovery of fiber area and muscle force production call into question the time course of nuclear repositioning. METHODS: We evaluated regeneration after cardiotoxin-induced damage in 10-week-old mice by quantifying intracellular and extracellular pathology at 2 and 94 weeks post-injection. RESULTS: Centrally nucleated fibers were still prevalent at 94 weeks post-injection, representing > 25% of muscle fibers. Areas with > 90% centrally nucleated fibers could still be identified. Extra-myocellular indicators of regeneration (e.g., fibrosis and fatty infiltration) also remained significantly elevated at the 94-week time-point. DISCUSSION: These findings indicate that not all nuclei are repositioned at the conclusion of induced muscle regeneration. Muscle Nerve 58:858-862, 2018.