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      Endothelial cell–oligodendrocyte interactions in small vessel disease and aging

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          Abstract

          Cerebral small vessel disease (SVD) is a prevalent, neurological disease that significantly increases the risk of stroke and dementia. The main pathological changes are vascular, in the form of lipohyalinosis and arteriosclerosis, and in the white matter (WM), in the form of WM lesions. Despite this, it is unclear to what extent the key cell types involved–the endothelial cells (ECs) of the vasculature and the oligodendrocytes of the WM–interact. Here, we describe the work that has so far been carried out suggesting an interaction between ECs and oligodendrocytes in SVD. As these interactions have been studied in more detail in other disease states and in development, we explore these systems and discuss the role these mechanisms may play in SVD.

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          Most cited references64

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          Claudin-1 and -2: Novel Integral Membrane Proteins Localizing at Tight Junctions with No Sequence Similarity to Occludin

          Occludin is the only known integral membrane protein localizing at tight junctions (TJ), but recent targeted disruption analysis of the occludin gene indicated the existence of as yet unidentified integral membrane proteins in TJ. We therefore re-examined the isolated junction fraction from chicken liver, from which occludin was first identified. Among numerous components of this fraction, only a broad silver-stained band ∼22 kD was detected with the occludin band through 4 M guanidine-HCl extraction as well as sonication followed by stepwise sucrose density gradient centrifugation. Two distinct peptide sequences were obtained from the lower and upper halves of the broad band, and similarity searches of databases allowed us to isolate two full-length cDNAs encoding related mouse 22-kD proteins consisting of 211 and 230 amino acids, respectively. Hydrophilicity analysis suggested that both bore four transmembrane domains, although they did not show any sequence similarity to occludin. Immunofluorescence and immunoelectron microscopy revealed that both proteins tagged with FLAG or GFP were targeted to and incorporated into the TJ strand itself. We designated them as “claudin-1” and “claudin-2”, respectively. Although the precise structure/function relationship of the claudins to TJ still remains elusive, these findings indicated that multiple integral membrane proteins with four putative transmembrane domains, occludin and claudins, constitute TJ strands.
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            Vascular niche for adult hippocampal neurogenesis.

            The thin lamina between the hippocampal hilus and granule cell layer, or subgranule zone (SGZ), is an area of active proliferation within the adult hippocampus known to generate new neurons throughout adult life. Although the neuronal fate of many dividing cells is well documented, little information is available about the phenotypes of cells in S-phase or how the dividing cells might interact with neighboring cells in the process of neurogenesis. Here, we make the unexpected observation that dividing cells are found in dense clusters associated with the vasculature and roughly 37% of all dividing cells are immunoreactive for endothelial markers. Most of the newborn endothelial cells disappear over several weeks, suggesting that neurogenesis is intimately associated with a process of active vascular recruitment and subsequent remodeling. The present data provide the first evidence that adult neurogenesis occurs within an angiogenic niche. This environment may provide a novel interface where mesenchyme-derived cells and circulating factors influence plasticity in the adult central nervous system. Copyright 2000 Wiley-Liss, Inc.
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              Classification and natural history of clinically identifiable subtypes of cerebral infarction.

              We describe the incidence and natural history of four clinically identifiable subgroups of cerebral infarction in a community-based study of 675 patients with first-ever stroke. Of 543 patients with a cerebral infarct, 92 (17%) had large anterior circulation infarcts with both cortical and subcortical involvement (total anterior circulation infarcts, TACI); 185 (34%) had more restricted and predominantly cortical infarcts (partial anterior circulation infarcts, PACI); 129 (24%) had infarcts clearly associated with the vertebrobasilar arterial territory (posterior circulation infarcts, POCI); and 137 (25%) had infarcts confined to the territory of the deep perforating arteries (lacunar infarcts, LACI). There were striking differences in natural history between the groups. The TACI group had a negligible chance of good functional outcome and mortality was high. More than twice as many deaths were due to the complications of immobility than to direct neurological sequelae of the infarct. Patients in the PACI group were much more likely to have an early recurrent stroke than were patients in other groups. Those in the POCI group were at greater risk of a recurrent stroke later in the first year after the index event but had the best chance of a good functional outcome. Despite the small anatomical size of the infarcts in the LACI group, many patients remained substantially handicapped. The findings have important implications for the planning of stroke treatment trials and suggest that various therapies could be directed specifically at the subgroups.
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                Author and article information

                Journal
                Clin Sci (Lond)
                Clin. Sci
                ppclinsci
                CS
                Clinical Science (London, England : 1979)
                Portland Press Ltd.
                0143-5221
                1470-8736
                15 February 2017
                1 March 2017
                : 131
                : 5 ( displayID: 5 )
                : 369-379
                Affiliations
                MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, EH16 4UU, U.K.
                Author notes
                Correspondence: Anna Williams (email anna.williams@ 123456ed.ac.uk )
                Article
                CS20160618
                10.1042/CS20160618
                5310718
                28202749
                57b408f1-755b-40d5-9e3c-73d96008f1c6
                © 2017 The Author(s)

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY).

                History
                : 10 October 2016
                : 28 November 2016
                : 14 December 2016
                Page count
                Figures: 1, References: 116, Pages: 11
                Categories
                Review Articles
                Review Article
                38
                40
                47

                Medicine
                dementia,endothelial cells,myelin,oligodendrocytes,small vessel disease
                Medicine
                dementia, endothelial cells, myelin, oligodendrocytes, small vessel disease

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