Neuropathologic evidence of endothelial changes in cerebral small vessel disease
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 endothelia...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1826259327404474368 |
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| author | Giwa, M Williams, J Elderfield, K Jiwa, N Bridges, L Kalaria, R Markus, H Esiri, M Hainsworth, A |
| author_facet | Giwa, M Williams, J Elderfield, K Jiwa, N Bridges, L Kalaria, R Markus, H Esiri, M Hainsworth, A |
| author_sort | Giwa, M |
| collection | OXFORD |
| description | 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. Copyright © 2012 by AAN Enterprises, Inc. |
| first_indexed | 2024-03-06T18:48:06Z |
| format | Journal article |
| id | oxford-uuid:0f3c2d1b-6065-438e-8b89-67cc96963bed |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:48:06Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:0f3c2d1b-6065-438e-8b89-67cc96963bed2022-03-26T09:50:17ZNeuropathologic evidence of endothelial changes in cerebral small vessel diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0f3c2d1b-6065-438e-8b89-67cc96963bedEnglishSymplectic Elements at Oxford2012Giwa, MWilliams, JElderfield, KJiwa, NBridges, LKalaria, RMarkus, HEsiri, MHainsworth, AObjectives: 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. Copyright © 2012 by AAN Enterprises, Inc. |
| spellingShingle | Giwa, M Williams, J Elderfield, K Jiwa, N Bridges, L Kalaria, R Markus, H Esiri, M Hainsworth, A Neuropathologic evidence of endothelial changes in cerebral small vessel disease |
| title | Neuropathologic evidence of endothelial changes in cerebral small vessel disease |
| title_full | Neuropathologic evidence of endothelial changes in cerebral small vessel disease |
| title_fullStr | Neuropathologic evidence of endothelial changes in cerebral small vessel disease |
| title_full_unstemmed | Neuropathologic evidence of endothelial changes in cerebral small vessel disease |
| title_short | Neuropathologic evidence of endothelial changes in cerebral small vessel disease |
| title_sort | neuropathologic evidence of endothelial changes in cerebral small vessel disease |
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