Long-term denervation in humans causes degeneration of both contractile and excitation-contraction coupling apparatus, which is reversible by functional electrical stimulation (FES): A role for myofiber regeneration?

Helmut Kern, Simona Boncompagni, Katia Rossini, Winfried Mayr, Giorgio Fanò, Maria Elena Zanin, Marzena Podhorska-Okolow, Feliciano Protasi, Ugo Carraro

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Over the last 30 years there has been considerable interest in the use of functional electrical stimulation (FES) to restore movement to the limbs of paralyzed patients. Spinal cord injury causes a rapid loss in both muscle mass and contractile force. The atrophy is especially severe when the injury involves lower motoneurons because many months after spinal cord injury, atrophy is complicated by fibrosis and fat substitution. In this study we describe the effects of long-term lower motoneuron denervation of human muscle and present the structural results of muscle trained using FES. By means of an antibody for embryonic myosin, we demonstrate that many regenerative events continue to spontaneously occur in human long-term denervated and degenerated muscle (DDM). In addition, using electron microscopy, we describe i) the overall structure of fibers and myofibrils in long-term denervated and degenerated muscle, including the effects of FES. and ii) the structure and localization of calcium release units, or triads; the structures reputed to activate muscle contraction during excitation-contraction coupling (ECC). Both apparatus undergo disarrangement and re-organization following long-term denervation and FES, respectively. The poor excitability of human long-term DDM fibers, which extends to the first periods of FES training, may be explained in terms of the spatial disorder of the ECC apparatus. Its disorganization and re-organization following long-term denervation and FES, respectively, may play a key role in the parallel disarrangement and re-organization of the myofibrils that characterize denervation and FES training. The present structural studies demonstrate that the protocol used during FES training is effective in reverting long-term denervation atrophy and dystrophy. The mean fiber diameter in FES biopsies is 42.2 ± 14.8 SD (p <0.0001 vs DDM 14.9 ± 6.0 SD); the mean percentile of myofiber area of the biopsy is 94.3 ± 5.7 SD (p <0.0001 vs DDM 25.7 ± 23.7 SD); the mean percentile fat area is 2.1 ± 2.4 SD (p <0.001 vs DDM 12.8 ± 12.1 SD); and the mean percentile connective tissue area is 3.6 ± 4.6 SD (p <0.001 vs DDM 61.6 ± 20.1 SD). In DDM biopsies more than 50% of myofibers have diameter smaller than 10 μm, while the FES-trained subjects have more that 50% of myofibers larger than 30 μm. The recovery of muscle mass seems to be the result of both a size increase of the surviving fibers and the regeneration of new myofibers.

Original languageEnglish
Pages (from-to)919-931
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume63
Issue number9
Publication statusPublished - Sep 2004

Fingerprint

Excitation Contraction Coupling
Denervation
Electric Stimulation
Regeneration
Muscles
Atrophy
Myofibrils
Motor Neurons
Spinal Cord Injuries
Biopsy
Fats
Muscle Denervation
Myosins
Muscle Contraction
Connective Tissue
Electron Microscopy
Fibrosis
Extremities

Keywords

  • Excitation-contraction coupling
  • Functional electrical stimulation
  • Human, long-term denervation
  • Lower motor neuron lesion
  • Myofiber regeneration
  • Spinal cord injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Long-term denervation in humans causes degeneration of both contractile and excitation-contraction coupling apparatus, which is reversible by functional electrical stimulation (FES) : A role for myofiber regeneration? / Kern, Helmut; Boncompagni, Simona; Rossini, Katia; Mayr, Winfried; Fanò, Giorgio; Zanin, Maria Elena; Podhorska-Okolow, Marzena; Protasi, Feliciano; Carraro, Ugo.

In: Journal of Neuropathology and Experimental Neurology, Vol. 63, No. 9, 09.2004, p. 919-931.

Research output: Contribution to journalArticle

Kern, Helmut ; Boncompagni, Simona ; Rossini, Katia ; Mayr, Winfried ; Fanò, Giorgio ; Zanin, Maria Elena ; Podhorska-Okolow, Marzena ; Protasi, Feliciano ; Carraro, Ugo. / Long-term denervation in humans causes degeneration of both contractile and excitation-contraction coupling apparatus, which is reversible by functional electrical stimulation (FES) : A role for myofiber regeneration?. In: Journal of Neuropathology and Experimental Neurology. 2004 ; Vol. 63, No. 9. pp. 919-931.
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abstract = "Over the last 30 years there has been considerable interest in the use of functional electrical stimulation (FES) to restore movement to the limbs of paralyzed patients. Spinal cord injury causes a rapid loss in both muscle mass and contractile force. The atrophy is especially severe when the injury involves lower motoneurons because many months after spinal cord injury, atrophy is complicated by fibrosis and fat substitution. In this study we describe the effects of long-term lower motoneuron denervation of human muscle and present the structural results of muscle trained using FES. By means of an antibody for embryonic myosin, we demonstrate that many regenerative events continue to spontaneously occur in human long-term denervated and degenerated muscle (DDM). In addition, using electron microscopy, we describe i) the overall structure of fibers and myofibrils in long-term denervated and degenerated muscle, including the effects of FES. and ii) the structure and localization of calcium release units, or triads; the structures reputed to activate muscle contraction during excitation-contraction coupling (ECC). Both apparatus undergo disarrangement and re-organization following long-term denervation and FES, respectively. The poor excitability of human long-term DDM fibers, which extends to the first periods of FES training, may be explained in terms of the spatial disorder of the ECC apparatus. Its disorganization and re-organization following long-term denervation and FES, respectively, may play a key role in the parallel disarrangement and re-organization of the myofibrils that characterize denervation and FES training. The present structural studies demonstrate that the protocol used during FES training is effective in reverting long-term denervation atrophy and dystrophy. The mean fiber diameter in FES biopsies is 42.2 ± 14.8 SD (p <0.0001 vs DDM 14.9 ± 6.0 SD); the mean percentile of myofiber area of the biopsy is 94.3 ± 5.7 SD (p <0.0001 vs DDM 25.7 ± 23.7 SD); the mean percentile fat area is 2.1 ± 2.4 SD (p <0.001 vs DDM 12.8 ± 12.1 SD); and the mean percentile connective tissue area is 3.6 ± 4.6 SD (p <0.001 vs DDM 61.6 ± 20.1 SD). In DDM biopsies more than 50{\%} of myofibers have diameter smaller than 10 μm, while the FES-trained subjects have more that 50{\%} of myofibers larger than 30 μm. The recovery of muscle mass seems to be the result of both a size increase of the surviving fibers and the regeneration of new myofibers.",
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T2 - A role for myofiber regeneration?

AU - Kern, Helmut

AU - Boncompagni, Simona

AU - Rossini, Katia

AU - Mayr, Winfried

AU - Fanò, Giorgio

AU - Zanin, Maria Elena

AU - Podhorska-Okolow, Marzena

AU - Protasi, Feliciano

AU - Carraro, Ugo

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