No abstract

CADASIL is a generalized angiopathy caused by mutations in NOTCH 3 gene leading to degeneration and loss of vascular smooth muscle cells (VSMC) in small arteries and arterioles. Since the receptor protein encoded by NOTCH 3 gene is expressed not only on VSMC but also on pericytes, pericytes and capillary vessels can be damaged by CADASIL. To check this hypothesis we examined microvessels in autopsy brains and skin-muscle biopsies of CADASIL patients. We found degeneration and loss of pericytes in capillary vessels. Pericytes were shrunken and their cytoplasm contained numerous vacuoles, big vesicular structures and complexes of enlarged pathological mitochondria. Degenerative changes were also observed within endothelial-pericytic connections, especially within peg-and-socket junctions. Nearby pericyte cell membranes or inside infoldings, deposits of granular osmiophilic material (GOM) were usually seen. In the affected capillaries endothelial cells revealed features of degeneration, selective death or swelling, leading to narrowing or occlusion of the capillary lumen. Our findings indicate that in CADASIL not only VSMC but also pericytes are severely damaged. Pericyte involvement in CADASIL can result in increased permeability of capillary vessels and disturbances in cerebral microcirculation, leading to white matter injury. Since in capillaries pericytes regulate vessel contractility, their degeneration can also cause defective vasomotor reactivity, the phenomenon observed very early in CADASIL, before development of histopathological changes in vessel walls.

No abstract

The process of β-amyloid accumulation in cerebral vessels is presented. Cerebral amyloid angiopathy (CAA) was confirmed during an autopsy. It was diagnosed according to the Boston criteria. Cerebral amyloid angiopathy can involve all kinds of cerebral vessels (cortical and leptomeningeal arterioles, capillaries and veins). The development of CAA is a progressive process. β-amyloid appears first in the tunica media, surrounding smooth muscle cells, and in the adventitia. β-amyloid is progressively accumulated, causing a gradual loss of smooth muscle cells in the vessel wall and finally replacing them. Then, the detachment and delamination of the outer part of the tunica media results in the "double barrel" appearance, fibrinoid necrosis, and microaneurysm formation. Microbleeding with perivascular deposition of erythrocytes and blood breakdown products can also occur. β-amyloid can also be deposited in the surrounding of the affected vessels of the brain parenchyma, known as "dysphoric CAA". Ultrastructurally, when deposits of amyloid fibers were localized in or outside the arteriolar wall, the degenerating vascular smooth muscle cells were observed. In the Institute of Psychiatry and Neurology the study was carried out in a group of 48 patients who died due to intracerebral hemorrhage caused by sporadic CAA.

Lectin selectins and their counter-receptors participate in discontinuous cell-cell interactions concurrent with leukocyte tethering and rolling on endothelium, which, in consequence, leads to leukocyte penetration to lymphatic organs and generation of inflammation sites. Counter-receptors are glycoproteins in which carbohydrate units, the direct selectin ligands, are built into the polypeptide framework. In this review, the distribution, structure and function of the main ligands and counter-receptors for P-, L- and E-selectins known so far, have been discussed. The common biosynthetic pathway of sialyl-Lewis x and sulpho-sialyl-Lewis x determinants of selectin ligands has been described.