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

Jianqin Niu^1,2, Hui-Hsin Tsai¹, Kimberly K Hoi¹

¹Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.

Nature Neuroscience

|April 17, 2019

Abstract:

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.

Insights

In multiple sclerosis (MS), oligodendrocyte precursor cells (OPCs) cluster around blood vessels, disrupting the blood-brain barrier (BBB) and worsening CNS inflammation. This interaction perpetuates MS disease progression.

Area of Science:

Neuroscience
Immunology
Cell Biology

Background:

Blood-brain barrier (BBB) disruption is a key factor in multiple sclerosis (MS) pathogenesis.
Understanding the interaction between brain cells and vasculature is crucial for MS research.

Purpose of the Study:

To investigate the interaction between oligodendroglia and vasculature in human MS white matter lesions.
To elucidate the mechanisms by which this interaction contributes to BBB disruption and CNS inflammation in MS.

Main Methods:

Analysis of human MS lesions.
Investigation of oligodendrocyte precursor cell (OPC) behavior and interaction with blood vessels.
Assessment of BBB integrity and CNS inflammation markers.

Main Results:

Perivascular clustering of OPCs observed in active MS lesions, indicating impaired detachment from vessels.
Perivascular OPCs disrupt the BBB by interfering with astrocyte endfeet and endothelial tight junctions.
Aberrant Wnt signaling in OPCs contributes to their dysfunctional vascular detachment and Wif1 secretion, further compromising BBB integrity.

Conclusions:

A defective oligodendroglial-vascular interaction in MS perpetuates the disease.
Aberrant OPC perivascular migration impairs lesion repair and actively disrupts the BBB, exacerbating CNS inflammation and MS progression.

Read full analysis

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