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The isothiocyanate sulforaphane modulates platelet function and protects against cerebral thrombotic dysfunction

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Title: The isothiocyanate sulforaphane modulates platelet function and protects against cerebral thrombotic dysfunction
Authors: Gillespie, S
Holloway, PM
Becker, F
Vital, SA
Taylor, KA
Stokes, KY
Emerson, M
Gavins, FNE
Item Type: Journal Article
Abstract: Background and purpose Platelet activation provides a critical link between inflammation and thrombosis. Sulforaphane (SFN), a naturally occurring isothiocyanate, has been shown to display both anti‐inflammatory and anti‐thrombotic actions in the systemic microvasculature. As inflammation promotes thrombosis and vice versa, this study investigates whether SFN is able to reduce inflammatory potentiation of thrombotic events, suppress platelet activation and thrombus formation in the cerebral microvasculature. Experimental approach Thrombosis was induced in the murine brain using the light/dye‐injury model, in conjunction with lipopolysaccharide (LPS) treatment, with and without SFN treatment. In vitro and in vivo platelet assays (aggregation, flow and other functional tests) were also employed, using both human and murine platelets. Key Results SFN was found to reduce LPS mediated enhancement of thrombus formation in the cerebral microcirculation. In tail bleed experiments LPS treatment prolonged bleeding time, and SFN treatment was found to protect against this LPS‐induced derangement of platelet function. SFN inhibited collagen‐mediated platelet aggregation in vitro and in vivo and the associated adhesion and impaired calcium signalling. Furthermore, Glycoprotein VI (GPVI) is involved in the protective effects observed with SFN treatment. Conclusions and Implications Data presented here provides evidence for the use of SFN in preventing stroke in selected high‐risk patient cohorts.
Issue Date: 1-Aug-2018
Date of Acceptance: 4-May-2018
URI: http://hdl.handle.net/10044/1/59839
DOI: https://dx.doi.org/10.1111/bph.14368
ISSN: 1476-5381
Publisher: Wiley
Start Page: 3333
End Page: 3346
Journal / Book Title: British Journal of Pharmacology
Volume: 175
Issue: 16
Copyright Statement: © 2018 The British Pharmacological Society
Sponsor/Funder: NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research)
Medical Research Council (MRC)
Funder's Grant Number: NC/M000079/1
MC_PC_12015
Keywords: Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
IN-VIVO
MICROVASCULAR THROMBOSIS
ENDOTHELIAL-CELLS
ARRIVE GUIDELINES
PLASMA-MEMBRANE
ANIMAL RESEARCH
CONCISE GUIDE
ACTIVATION
AGGREGATION
ASSOCIATION
Pharmacology & Pharmacy
1115 Pharmacology and Pharmaceutical Sciences
Publication Status: Published
Online Publication Date: 2018-05-24
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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