Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis

J Neuropathol Exp Neurol. 2006 Sep;65(9):855-65. doi: 10.1097/01.jnen.0000235119.52311.16.

Abstract

Dysferlin is a muscle protein involved in cell membrane repair and its deficiency is associated with muscular dystrophy. We describe that dysferlin is also expressed in leaky endothelial cells. In the normal central nervous system (CNS), dysferlin is only present in endothelial cells of circumventricular organs. In the inflamed CNS of patients with multiple sclerosis (MS) or in animals with experimental autoimmune encephalomyelitis, dysferlin reactivity is induced in endothelial cells and the expression is associated with vascular leakage of serum proteins. In MS, dysferlin expression in endothelial cells is not restricted to vessels with inflammatory cuffs but is also present in noninflamed vessels. In addition, many blood vessels with perivascular inflammatory infiltrates lack dysferlin expression in inactive lesions or in the normal-appearing white matter. In vitro, dysferlin can be induced in endothelial cells by stimulation with tumor necrosis factor-alpha. Hence, dysferlin is not only a marker for leaky brain vessels, but also reveals dissociation of perivascular inflammatory infiltrates and blood-brain barrier disturbance in multiple sclerosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Dysferlin
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Fibrin / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / diagnosis*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Nerve Tissue Proteins / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Inbred Lew
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Vascular Diseases / diagnosis*
  • Vascular Diseases / pathology

Substances

  • Biomarkers
  • DYSF protein, human
  • Dysf protein, mouse
  • Dysferlin
  • Membrane Proteins
  • Muscle Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Fibrin