Muscle contractures in patients with cerebral palsy and acquired brain injury are associated with extracellular matrix expansion, pro-inflammatory gene expression, and reduced rRNA synthesis

Muscle Nerve. 2018 Aug;58(2):277-285. doi: 10.1002/mus.26130. Epub 2018 May 24.

Abstract

Introduction: Children with cerebral palsy (CP) and acquired brain injury (ABI) commonly develop muscle contractures with advancing age. An underlying growth defect contributing to skeletal muscle contracture formation in CP/ABI has been suggested.

Methods: The biceps muscles of children and adolescents with CP/ABI (n = 20) and typically developing controls (n = 10) were investigated. We used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting to assess gene expression relevant to growth and size homeostasis.

Results: Classical pro-inflammatory cytokines and genes involved in extracellular matrix (ECM) production were elevated in skeletal muscle of children with CP/ABI. Intramuscular collagen content was increased and satellite cell number decreased and this was associated with reduced levels of RNA polymerase I transcription factors, 45s pre-rRNA and 28S rRNA.

Discussion: The present study provides novel data suggesting a role for pro-inflammatory cytokines and reduced ribosomal production in the development/maintenance of muscle contractures, possibly underlying stunted growth and perimysial ECM expansion. Muscle Nerve 58: 277-285, 2018.

Keywords: cerebral palsy; cytokine; extracellular matrix; ribosome biogenesis; skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Brain Injuries / pathology*
  • Cell Count
  • Cerebral Palsy / pathology*
  • Child
  • Collagen / metabolism
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Extracellular Matrix / pathology*
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / pathology*
  • RNA, Ribosomal / biosynthesis*
  • RNA, Ribosomal / genetics
  • Real-Time Polymerase Chain Reaction
  • Ribosomes / genetics
  • Ribosomes / pathology
  • Satellite Cells, Skeletal Muscle / pathology

Substances

  • Cytokines
  • RNA, Ribosomal
  • Collagen