title: Atrophy-resistant fibers in permanent peripheral denervation of human skeletal muscle.
abstract: OBJECTIVE
  Human muscle fibers usually undergo severe atrophy/degeneration as a result of long-term peripheral denervation. However, some biopsies from paraplegic patients suffering complete conus cauda syndrome display the presence of a small percentage of muscle fibers with a very large diameter (big fibers). The objective of the present study is to determine if these big fibers are the result of residual innervation/reinnervation, or if instead they are fibers resistant to atrophy.
  
  
  METHODS
  Human muscle biopsies were harvested from the vastus lateralis of spinal cord injury (SCI) patients affected by complete lower motor neuron lesion (LML). The specimens were either processed for light microscopy or embedded for electron microscopy (EM).
  
  
  RESULTS
  Our results indicate that the big fibers are neither the results of residual innervation or sparse reinnervation. In spite of the fact that the extrasynaptic NCAM immunostaining disappear a few months after SCI, the big fibers are characterized by positive molecular markers of denervation, that is, the differential labeling of their dystrophin molecule by anti-C and anti-N terminals antibodies. Furthermore, the EM analysis shows that these cells present the peculiar ultrastructural disarrangements of the contractile apparatus and of the internal membrane systems characteristic of 'peripheral denervation'. No fibers presenting large areas of cross-striation were found. The EM analysis provides the final evidence that these big fibers are muscle fibers which are indeed denervated, very different from normal and/or disused (e.g. upper motor neuron lesion) muscle fibers.
  
  
  CONCLUSIONS
  Although these large muscle fibers are surprisingly more frequent in human muscle biopsies after 3 years from SCI than earlier, it remains to be determined whether their presence in some biopsies but not in others is caused by sampling, or is related to other factors such as to subjects' background genetics, or the extent of passive stretching induced by different rehabilitation strategies.
authors.affiliation: Italian C.N.R. Institute of Neuroscience, and Laboratory of Translational Myology, Interdepartmental Research Center of Myology, c/o Department of Biomedical Sciences, University of Padova, I-35121 Padova, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Biral
authors.forename: Helmut
authors.initials: H
authors.lastname: Kern
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Adami
authors.forename: Simona
authors.initials: S
authors.lastname: Boncompagni
authors.forename: Feliciano
authors.initials: F
authors.lastname: Protasi
authors.forename: Ugo
authors.initials: U
authors.lastname: Carraro
mesh_terms: D000328:Adult; D016189:Dystrophin / Q000378:metabolism; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000473:pathology*
chemical_list: D016189:Dystrophin