Vascular inflammation in cerebral small vessel disease

Abstract

Cerebral small vessel disease (CSVD) is considered to be caused by an increased permeability of the blood-brain barrier and results in enlargement of Virchow Robin spaces (VRs), white matter lesions, brain microbleeds, and lacunar infarcts. The increased permeability of the blood-brain barrier may relate to endothelial cell activation and activated monocytes/macrophages. Therefore, we hypothesized that plasma markers of endothelial activation (adhesion molecules) and monocyte/macrophage activation (neopterin) relate to CSVD manifestations. In 163 first-ever lacunar stroke patients and 183 essential hypertensive patients, we assessed CSVD manifestations on brain magnetic resonance imaging (MRI) and levels of C-reactive protein (CRP), neopterin, as well as circulating soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin). Neopterin, sICAM-1 and sVCAM-1 levels were higher in patients with extensive CSVD manifestations than in those without (p < 0.01). Neopterin levels independently related to higher numbers of enlarged Virchow Robin spaces (p < 0.001). An inflammatory process with activated monocytes/macrophages may play a role in the increased permeability of the blood brain barrier in patients with CSVD.

Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

“…Very few studies used cellular biomarkers of endothelial dysfunction. Finally, with the exception of a few studies, 52,66,74,79,84 only selective biomarkers involved in different points of the complex pathways linking together endothelial dysfunction and coagulation system/inflammation processes were analyzed. It should be underlined that the assessment of individual biomarkers cannot provide information on relative contributions by the distinct pathways.…”

“…76 Interestingly, in the Austrian Stroke Prevention Study, ICAM-1 proved to be associated with a robust outcome measure, i.e., WMH progression at both 3 and 6 years. 85 Rouhl et al 84 studied several endothelial biomarkers finding higher levels of E-selectine, neopterin, and VCAM-1 in patients with lacunar infarcts and/or WMH. Considering MRI markers of SVD, PVS resulted independently associated with neopterin and MB with E-selectine.…”

Emerging Evidence for Pathogenesis of Sporadic Cerebral Small Vessel Disease

“…33 Another environmental factor, inflammation (namely, chronic inflammation) is also related to SVD pathology (Figure 1), including lacunar stroke, enlarged perivascular space, and subsequent WMH. 34,35 Consequently, many studies have focused on the relationship between inflammation and SVD. It has been demonstrated that inflammation primarily targets endothelial cells and results in BBB breakdown, 36,37 probably because of neopterin and cytokines secreted by activated monocytes/ macrophages, 34 subsequently disrupting the extracellular matrix.…”

“…34,35 Consequently, many studies have focused on the relationship between inflammation and SVD. It has been demonstrated that inflammation primarily targets endothelial cells and results in BBB breakdown, 36,37 probably because of neopterin and cytokines secreted by activated monocytes/ macrophages, 34 subsequently disrupting the extracellular matrix. 38 The question is what triggers inflammation in the first place?…”

Hypertension: an autoimmune disease?

“…9 Indeed, we recently demonstrated that immunoglobulin G antibodies to oxidized low-density lipoproteins were elevated in patients with cerebral small vessel disease as compared with patients with uncomplicated hypertension. 10 Interestingly, protective immunoglobulin M antibodies were lower in patients with cerebral small vessel disease as compared with uncomplicated hypertension patients.…”