RGD Reference Report - Neuropathologic evidence of endothelial changes in cerebral small vessel disease. - Rat Genome Database

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Neuropathologic evidence of endothelial changes in cerebral small vessel disease.

Authors: Giwa, MO  Williams, J  Elderfield, K  Jiwa, NS  Bridges, LR  Kalaria, RN  Markus, HS  Esiri, MM  Hainsworth, AH 
Citation: Giwa MO, etal., Neurology. 2011 Dec 14.
RGD ID: 5684978
Pubmed: (View Article at PubMed) PMID:22170884
DOI: Full-text: DOI:10.1212/WNL.0b013e3182407968

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.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Thbd  (thrombomodulin)

Genes (Mus musculus)
Thbd  (thrombomodulin)

Genes (Homo sapiens)
THBD  (thrombomodulin)


Additional Information