Rapid diaphragm atrophy following cervical spinal cord hemisection

Respir Physiol Neurobiol. 2014 Feb 1:192:66-73. doi: 10.1016/j.resp.2013.12.006. Epub 2013 Dec 14.

Abstract

A cervical (C2) hemilesion (C2Hx), which disrupts ipsilateral bulbospinal inputs to the phrenic nucleus, was used to study diaphragm plasticity after acute spinal cord injury. We hypothesized that C2Hx would result in rapid atrophy of the ipsilateral hemidiaphragm and increases in mRNA expression of proteolytic biomarkers. Diaphragm tissue was harvested from male Sprague-Dawley rats at 1 or 7 days following C2Hx. Histological analysis demonstrated reduction in cross-sectional area (CSA) of type I and IIa fibers in the ipsilateral hemidiaphragm at 1 but not 7 days. Type IIb/x fibers, however, had reduced CSA at 1 and 7 days. A targeted gene array was used to screen mRNA changes for genes associated with skeletal muscle myopathy and myogenesis; this was followed by qRT-PCR validation. Changes in diaphragm gene expression suggested that profound myoplasticity is initiated immediately following C2Hx including activation of both proteolytic and myogenic pathways. We conclude that an immediate myoplastic response occurs in the diaphragm after C2Hx with atrophy occurring in ipsilateral myofibers within 1 day.

Keywords: Atrophy; Diaphragm; Genes; Proteolysis; Spinal cord injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diaphragm / metabolism
  • Diaphragm / pathology*
  • Functional Laterality*
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology
  • Male
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscular Atrophy, Spinal / etiology*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome, Newborn / etiology*
  • Spinal Cord Injuries / complications*
  • Time Factors

Substances

  • Cytokines
  • Muscle Proteins
  • RNA, Messenger

Supplementary concepts

  • Spinal muscular atrophy with respiratory distress 1