Central nervous system endothelium in neuroinflammatory, neuroinfectious, and neurodegenerative disease

Andjelkovic, Anuska V.; Pachter, Joel S.

doi:10.1002/(sici)1097-4547(19980215)51:4<423::aid-jnr2>3.0.co;2-e

Cited by 33 publications

(15 citation statements)

References 68 publications

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“…Increasing evidence has demonstrated that pathological changes in the microvasculature play a role in neurodegenerative diseases and especially in AD (Andjelkovic and Pachter 1998). Elevated levels of pro-inflammatory cytokines, such as TNF-α and IL-1β, have been found to be released by microvessels in the AD brain as compared to microvessels from age-matched controls (Grammas and Ovase 2001).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Human Brain Microvascular Endothelial Cell Adhesion and Barrier Functions by Memantine

et al. 2017

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Vascular risk factors have been linked to cognitive decline and dementia in the elderly. Microvascular inflammation, especially of the endothelium, may contribute to the progression of neurodegenerative events in Alzheimer's disease (AD). Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is a licensed drug used for the treatment of moderate to severe AD. However, little information is available regarding its anti-inflammatory effects on the endothelium. In this study, we investigated the effects of memantine on human brain microvascular endothelial dysfunction induced by the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Our results show that memantine prevents the attachment of monocyte THP-1 cells to human brain microvascular endothelial cells (HBMVEs). An in vitro BBB model experiment displayed that memantine could rescue TNF-α-induced disruption of the in vitro BBB model. In addition, memantine also interferes with monocyte transmigration across the BBB model. Our results indicate that TNF-α significantly increased the expression of cell adhesion molecules, such as ICAM-1, VCAM-1, and E-selectin, which was prevented by pretreatment with memantine. Mechanistically, memantine reversed activation of the transcription factor NF-κB by preventing the phosphorylation and degradation of its inhibitor IκBα. Our data is the first to describe a novel anti-inflammatory mechanism driven by the endothelial cell-mediated neuroprotective effects of memantine.

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Section: Discussionmentioning

confidence: 99%

Regulation of Human Brain Microvascular Endothelial Cell Adhesion and Barrier Functions by Memantine

et al. 2017

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“…Due to their critical role as regulators of cerebral homeostasis, perturbations of the microvascular endothelium are closely linked to the pathophysiology of neuroinflammatory and neurodegenerative disease states, including AD [178][179][180].…”

Section: Microvascular Endothelium As Mediator Of Inflammatory Processesmentioning

confidence: 99%

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Marco

Venneri

Farkas

et al. 2015

Neurobiology of Disease

231

185

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Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request.

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“…Similar events occur in psoriatic skin, where ECs actively display adhesion molecule for leukocyte recruitment, form new vessels, and mediate inflammation (94). In multiple sclerosis, transendothelial migration of activated leukocytes is one of the earliest abnormalities, and exposure of the endothelium to immune cell-derived IFN-␥, TNF-␣, and IL-1␤ disrupts the blood-brain barrier by disorganizing cell-cell junctions, enhancing leukocyte endothelial adhesion and migration, and increasing expression of MHC class II Ags (95). The endothelium promotes gut inflammation through comparable mechanisms.…”

Section: Ec-mediated Immune Dysfunction and Diseasementioning

confidence: 99%

Immune Regulation by Microvascular Endothelial Cells: Directing Innate and Adaptive Immunity, Coagulation, and Inflammation

Danese¹,

Dejana

Fiocchi

2007

The Journal of Immunology

256

203

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An effective immune response depends not only on the proper activation, regulation, and function of immune cells, but also on their distribution and retention in diverse tissue microenvironments where they encounter a number of stimuli and other cell types. These activities are mediated by endothelial cells, which form specialized microcirculatory networks used by immune cells under both physiological and pathological circumstances. Endothelial cells represent a highly heterogeneous population of cells with the ability to interact with and modulate the function of immune cells. This review is focused on the role of microvascular endothelial cells in innate and adaptive immunity, inflammation, coagulation, angiogenesis, and the therapeutic implications of targeting endothelial cells in selected autoimmune and chronic inflammatory disorders.

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Central nervous system endothelium in neuroinflammatory, neuroinfectious, and neurodegenerative disease

Cited by 33 publications

References 68 publications

Regulation of Human Brain Microvascular Endothelial Cell Adhesion and Barrier Functions by Memantine

Regulation of Human Brain Microvascular Endothelial Cell Adhesion and Barrier Functions by Memantine

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Immune Regulation by Microvascular Endothelial Cells: Directing Innate and Adaptive Immunity, Coagulation, and Inflammation

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