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In cerebral small vessel disease (arteriolosclerosis;\n                    <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content>\n                    ), the endothelial cells in small arteries survive, even when mural pathology is advanced and myocytes are severely depleted. Here, we review aspects of altered endothelial functions that have been implicated in\n                    <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content>\n                    : local\n                    <jats:styled-content style=\"fixed-case\">CBF<\/jats:styled-content>\n                    dysregulation, endothelial activation and blood\u2013brain barrier (\n                    <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>\n                    ) dysfunction. Reduced\n                    <jats:styled-content style=\"fixed-case\">CBF<\/jats:styled-content>\n                    is reported in the diffuse white matter lesions that are a neuroradiological signature of\n                    <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content>\n                    . This may reflect an underlying deficit in local\n                    <jats:styled-content style=\"fixed-case\">CBF<\/jats:styled-content>\n                    regulation (possibly via the nitric oxide\/\n                    <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\n                    signaling pathway). While many laboratories have observed an association of symptomatic\n                    <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content>\n                    with serum markers of endothelial activation, it is apparent that the origin of these circulating markers need not be brain endothelium. Our own neuropathology studies did not confirm local endothelial activation in small vessels exhibiting\n                    <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content>\n                    . Local\n                    <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>\n                    failure has been proposed as a cause of\n                    <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content>\n                    and associated parenchymal lesions. Some groups find that computational analyses of magnetic resonance imaging (\n                    <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>\n                    ) scans, following systemic injection of a gadolinium\u2010based contrast agent, suggest that extravasation into brain parenchyma is heightened in people with\n                    <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content>\n                    . Our recent histochemical studies of donated brain tissue, using immunolabeling for large plasma proteins [fibrinogen, immunoglobulin\n                    <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">IgG<\/jats:styled-content>\n                    )], do not support an association of\n                    <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content>\n                    with recent plasma protein extravasation. It is possible that a trigger leakage episode, or a size\u2010selective loosening of the\n                    <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>\n                    , participates in\n                    <jats:styled-content style=\"fixed-case\">SVD<\/jats:styled-content>\n                    pathology.\n                  <\/jats:p>","DOI":"10.1111\/bpa.12224","type":"journal-article","created":{"date-parts":[[2014,12,21]],"date-time":"2014-12-21T19:28:15Z","timestamp":1419190095000},"page":"44-50","source":"Crossref","is-referenced-by-count":99,"title":["Endothelial Cells and Human Cerebral Small Vessel Disease"],"prefix":"10.1111","volume":"25","author":[{"given":"Atticus H.","family":"Hainsworth","sequence":"first","affiliation":[{"name":"Molecular and Cellular Biology Research Centre St Georges University of London London UK"},{"name":"Stroke and Dementia Research Centre St Georges University of London London 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