Impaired blood-brain/spinal cord barrier in ALS patients

Brain Res. 2012 Aug 21;1469:114-28. doi: 10.1016/j.brainres.2012.05.056. Epub 2012 Jun 27.


Vascular pathology, including blood-brain/spinal cord barrier (BBB/BSCB) alterations, has recently been recognized as a key factor possibly aggravating motor neuron damage, identifying a neurovascular disease signature for ALS. However, BBB/BSCB competence in sporadic ALS (SALS) is still undetermined. In this study, BBB/BSCB integrity in postmortem gray and white matter of medulla and spinal cord tissue from SALS patients and controls was investigated. Major findings include (1) endothelial cell damage and pericyte degeneration, (2) severe intra- and extracellular edema, (3) reduced CD31 and CD105 expressions in endothelium, (4) significant accumulation of perivascular collagen IV, and fibrin deposits (5) significantly increased microvascular density in lumbar spinal cord, (6) IgG microvascular leakage, (7) reduced tight junction and adhesion protein expressions. Microvascular barrier abnormalities determined in gray and white matter of the medulla, cervical, and lumbar spinal cord of SALS patients are novel findings. Pervasive barrier damage discovered in ALS may have implications for disease pathogenesis and progression, as well as for uncovering novel therapeutic targets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / diagnostic imaging
  • Amyotrophic Lateral Sclerosis / pathology*
  • Blood-Brain Barrier / diagnostic imaging
  • Blood-Brain Barrier / pathology*
  • Disease Progression
  • Endothelial Cells / pathology
  • Endothelial Cells / ultrastructure
  • Female
  • Humans
  • Male
  • Medulla Oblongata / diagnostic imaging
  • Medulla Oblongata / pathology*
  • Middle Aged
  • Spinal Cord / diagnostic imaging
  • Spinal Cord / pathology*
  • Tight Junctions / pathology
  • Tight Junctions / ultrastructure
  • Ultrasonography