Reversal of endothelial dysfunction reduces white matter vulnerability in cerebral small vessel disease in rats

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Science Translational Medicine  04 Jul 2018:
Vol. 10, Issue 448, eaam9507
DOI: 10.1126/scitranslmed.aam9507

Defeating dysfunction

Cerebral small vessel disease (SVD) affects arterioles in the brain, increasing risk of stroke and causing symptoms of dementia. To understand the link between vascular changes and white matter pathology, Rajani and colleagues studied a rat model of SVD. Vascular tight junctions were impaired in SVD, and dysfunctional endothelial cells prevented oligodendrocyte precursors from maturing into myelinating cells. SVD rats had a mutation in an ATPase, which was also found in SVD human brain tissue. Drugs that stabilized endothelial cells could reverse the white matter abnormalities in early-stage SVD in the rat model, suggesting a potential therapeutic approach.

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