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Lookup NU author(s): Professor Raj KalariaORCiD
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Objectives: Cerebral small vessel disease (SVD) is common in aged brains and causes lacunar stroke, diffuse white matter lesions (leukoaraiosis), and vascular cognitive impairment. The pathogenesis is unknown. Endothelial dysfunction is a possible causal factor, and circulating markers of endothelial activation (intercellular adhesion molecule-1, thrombomodulin) and inflammation (interleukin [IL]-6) are elevated in patients with SVD. In this case-control study, we tested whether brain endothelial ICAM1, thrombomodulin, and IL-6 are altered in SVD. Methods: We examined small penetrating cerebral arteries of pathologically diagnosed SVD cases, aged controls without SVD, young control cases with no brain pathology, and cases with early-onset hereditary SVD (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]). All tissues had minimal cerebral amyloid angiopathy or other Alzheimer pathology. Results: Thrombomodulin immunoreactivity was present in all aged SVD, aged control, and CADASIL cases, primarily in small artery endothelium. Thrombomodulin was augmented in aged SVD cases compared with aged controls (p = 0.012) and in vessels with higher sclerotic index (an indicator of SVD severity; p = 0.01). Thrombomodulin was sparse/absent in young controls. Endothelial ICAM1 and IL-6 were rarely seen, and were not related to SVD. Conclusions: Our data suggest that cerebral endothelial activation in deep penetrating arteries is not associated with SVD. Endothelial thrombomodulin increased with SVD severity, and CADASIL data suggest that this may be a cerebral response to SVD. Elevated thrombomodulin may be a protective agent in SVD. Our data confirm endothelial involvement in SVD. Neurology (R) 2012;78:167-174
Author(s): Giwa MO, Williams J, Elderfield K, Jiwa NS, Bridges LR, Kalaria RN, Markus HS, Esiri MM, Hainsworth AH
Publication type: Article
Publication status: Published
Journal: Neurology
Year: 2012
Volume: 78
Issue: 3
Pages: 167-174
Print publication date: 17/01/2012
ISSN (print): 0028-3878
ISSN (electronic): 1526-632X
Publisher: Lippincott Williams & Wilkins
URL: http://dx.doi.org/10.1212/WNL.0b013e3182407968
DOI: 10.1212/WNL.0b013e3182407968
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