Department of Neurology, University of California at San Francisco, San Francisco
Aberrant oligodendroglial-vascular interactions disrupt the blood-brain barrier, triggering CNS inflammation
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.
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Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences , University at Buffalo, State University of New York , Buffalo
Vascular aspects of multiple sclerosis: emphasis on perfusion and cardiovascular comorbidities
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. Over the last two decades, more favorable MS long-term outcomes have contributed toward increase in prevalence of the aged MS population. Emergence of age-associated pathology, such as cardiovascular diseases, may interact with the MS pathophysiology and further contribute to disease progression. Areas covered: This review summarizes the cardiovascular involvement in MS pathology, its disease activity, and progression. The cardiovascular health, the presence of various cardiovascular diseases, and their effect on MS cognitive performance are further explored. In similar fashion, the emerging evidence of a higher incidence of extracranial arterial pathology and its association with brain MS pathology are discussed. Finally, the authors outline the methodologies behind specific perfusion magnetic resonance imaging (MRI) and ultrasound Doppler techniques, which allow measurement of disease-specific and age-specific vascular changes in the aging population and MS patients. Expert opinion: Cardiovascular pathology significantly contributes to worse clinical and MRI-derived disease outcomes in MS. Global and regional cerebral hypoperfusion may be associated with poorer physical and cognitive performance. Prevention, improved detection, and treatment of the cardiovascular-based pathology may improve the overall long-term health of MS patients.
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