Cromolyn administration (to block mast cell degranulation) reduces necrosis of dystrophic muscle in mdx mice

Neurobiol Dis. 2006 Aug;23(2):387-97. doi: 10.1016/j.nbd.2006.03.016. Epub 2006 Jun 23.

Abstract

Duchenne muscular dystrophy is a lethal muscle wasting disorder, resulting from mutations in the gene encoding for the skeletal muscle protein dystrophin. The absence of functional dystrophin leaves the muscle membrane vulnerable to damage during contraction. Damage initially occurs as 'tears' in the membrane, this damage can be exacerbated by the inflammatory response leading to myofibre necrosis rather than repair. Mast cells resident within skeletal muscle represent an immediate source of pro-inflammatory cytokines. We hypothesise that blockade of mast cell degranulation would reduce the extent of myofibre necrosis in the mdx mouse. Daily cromolyn injections were performed on young and exercised adult mdx mice and histological analysis confirmed that mast cell degranulation contributes to myofibre necrosis. This research identified high biological variation between individual mdx mice in the severity of the dystrophic pathology, and supported a relationship between extent of muscle damage in adult mdx mice and their individual enthusiasm for voluntary wheel running.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cromolyn Sodium / therapeutic use*
  • Mast Cells / drug effects
  • Mast Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / pathology
  • Muscular Dystrophy, Animal / drug therapy*
  • Muscular Dystrophy, Animal / pathology
  • Necrosis
  • Neutrophils / drug effects
  • Neutrophils / physiology

Substances

  • Cromolyn Sodium