Impairment of tight junctions and glucose transport in endothelial cells of human cerebral cavernous malformations

J Neuropathol Exp Neurol. 2011 Jun;70(6):417-29. doi: 10.1097/NEN.0b013e31821bc40e.


Cerebral cavernous malformations (CCMs) often cause hemorrhages that can result in severe clinical manifestations, including hemiparesis and seizures. The underlying mechanisms of the aggressive behavior of CCMs are undetermined to date, but alterations of vascular matrix components may be involved. We compared the localization of the tight junction proteins (TJPs) in 12 CCM specimens and the expression of glucose transporter 1 (GLUT-1), which is sensitive to alterations in TJP levels, in 5 CCM specimens with those in 5 control temporal lobectomy specimens without CCM by immunofluorescence microscopy. The TJPs occludin, claudin-5, and zonula occludens ZO-1 were downregulated at intercellular contact sites and partly redistributed within the surrounding tissue in the CCM samples; there was also a marked reduction of GLUT-1 immunoreactivity compared with that in control specimens. Corresponding analysis using quantitative real-time reverse transcription polymerase chain reaction on 8 CCM and 8 control specimens revealed significant downregulation of mRNA expression of occludin, claudin-5, ZO-1, and GLUT-1. The altered expression and localization of the TJPs at interendothelial contact sites accompanied by a reduction of GLUT-1 expression in dilated CCM microvessels likely affect vascular matrix stability and may contribute to hemorrhages of CCMs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Central Nervous System Vascular Malformations / metabolism
  • Central Nervous System Vascular Malformations / pathology*
  • Central Nervous System Vascular Malformations / physiopathology
  • Child
  • Claudin-5
  • Down-Regulation / physiology
  • Endothelial Cells / metabolism*
  • Female
  • Glucose / metabolism
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism*
  • Humans
  • Intercellular Junctions / genetics
  • Intercellular Junctions / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Middle Aged
  • Occludin
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • RNA, Messenger / metabolism
  • Tight Junctions / metabolism
  • Tight Junctions / pathology*
  • Young Adult
  • Zonula Occludens-1 Protein


  • CLDN5 protein, human
  • Claudin-5
  • Glucose Transporter Type 1
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Phosphoproteins
  • RNA, Messenger
  • SLC2A1 protein, human
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • Glucose