Structural differentiation of skeletal muscle fibers in the absence of innervation in humans

Abstract

The relative importance of muscle activity versus neurotrophic factors in the maintenance of muscle differentiation has been greatly debated. Muscle biopsies from spinal cord injury patients, who were trained with an innovative protocol of functional electrical stimulation (FES) for prolonged periods (2.4 -9.3 years), offered the unique opportunity of studying the structural recovery of denervated fibers from severe atrophy under the sole influence of muscle activity. FES stimulation induced surprising recovery of muscle structure, mass, and force even in patients whose muscles had been denervated for prolonged periods before the beginning of FES training (up to 2 years) and had almost completely lost muscle-specific internal organization. Ninety percent (or more) of the fibers analyzed by electron microscopy showed a striking recovery of the ultrastructural organization of myofibrils and Ca 2؉ -handling membrane systems. This functional/structural restoration follows a pattern that mimics some aspects of normal muscle differentiation. Most importantly, the recovery occurs in the complete absence of motor and sensory innervation and of nerve-derived trophic factors, that is, solely under the influence of muscle activity induced by electrical stimulation.atrophy ͉ denervation ͉ spinal cord injury

Medical image analysis and 3-d modeling to quantify changes and functional restoration in denervated muscle undergoing electrical stimulation treatment

“…Important benefits for the patients are the improved cosmetic appearance of lower extremities, the enhanced cushioning effect for seating and the early result of impressive reduction of the leg edema [9,10]. The last observation is supported by changes of the capillary networks observed in the muscle biopsies harvested from subjects suffering with long-lasting LMN denervation before and after h-b ES and thoracic level SCI [11].…”

Severely Atrophic Muscle Fibers with Nuclear Clumps Survive many Years in Permanently Denervated Human Muscle

“…Nuclear clumps should be considered markers of the long-lasting ability of human muscle fibers to survive to the absence of the nerve. These results provide the rationale to plan research aimed to recover these severely atrophic myofibers, by combining molecular and cellular approaches with functional electrical stimulation that our previous studies shown to restore muscle structure and mass in human long-term denervated and degenerated muscle [4,7,[15][16][17][18][19][20].…”

Scientific Discoveries: What Is Required for Lasting Impact

“…If, on the other hand, neurotrophic substances are essential, such prospects seem less likely" (115). Since then, much effort has been made by researchers in Vienna to develop apparatuses and methods for percutaneous long-term stimulation of denervated leg muscles in humans with complete and irreversible lower motor neuron destruction (116)(117)(118). After 2 years of stimulation, remarkable improvements are observed in muscle mass, fiber diameter, ultrastructure, tissue composition, and muscle force, with some parameters reaching normal values and 25% of patients able to perform stimulation-assisted stand-up exercises.…”