Aberrant oligodendroglial-vascular interactions disrupt the blood-brain barrier, triggering CNS inflammation

Nat Neurosci. 2019 May;22(5):709-718. doi: 10.1038/s41593-019-0369-4. Epub 2019 Apr 15.


Disruption of the blood-brain barrier (BBB) is critical to initiation and perpetuation of disease in multiple sclerosis (MS). We report an interaction between oligodendroglia and vasculature in MS that distinguishes human white matter injury from normal rodent demyelinating injury. We find perivascular clustering of oligodendrocyte precursor cells (OPCs) in certain active MS lesions, representing an inability to properly detach from vessels following perivascular migration. Perivascular OPCs can themselves disrupt the BBB, interfering with astrocyte endfeet and endothelial tight junction integrity, resulting in altered vascular permeability and an associated CNS inflammation. Aberrant Wnt tone in OPCs mediates their dysfunctional vascular detachment and also leads to OPC secretion of Wif1, which interferes with Wnt ligand function on endothelial tight junction integrity. Evidence for this defective oligodendroglial-vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Astrocytes / pathology
  • Astrocytes / physiology
  • Blood-Brain Barrier / pathology
  • Blood-Brain Barrier / physiopathology*
  • Cell Movement
  • Cells, Cultured
  • Encephalitis / pathology
  • Encephalitis / physiopathology*
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology*
  • Oligodendrocyte Precursor Cells / pathology
  • Oligodendrocyte Precursor Cells / physiology*
  • Tight Junctions / metabolism
  • White Matter / pathology


  • Adaptor Proteins, Signal Transducing
  • Extracellular Matrix Proteins
  • Intercellular Signaling Peptides and Proteins
  • Wif1 protein, mouse