Journal article
The isothiocyanate sulforaphane modulates platelet function and protects against cerebral thrombotic dysfunction
- Abstract:
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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, in this study we investigated 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 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 was shown to be involved in the protective effects observed with SFN treatment.
Conclusions and Implications The data presented here provide evidence for the use of SFN in preventing stroke in selected high-risk patient cohorts.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, pdf, 1.1MB, Terms of use)
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(Supplementary materials, tiff, 2.0MB, Terms of use)
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- Publisher copy:
- 10.1111/bph.14368
Authors
- Publisher:
- Wiley
- Journal:
- British Journal of Pharmacology More from this journal
- Volume:
- 175
- Issue:
- 16
- Pages:
- 3333-3346
- Place of publication:
- England
- Publication date:
- 2018-07-03
- Acceptance date:
- 2018-05-04
- DOI:
- EISSN:
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1476-5381
- ISSN:
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0007-1188
- Pmid:
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29797311
- Language:
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English
- Pubs id:
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892613
- Local pid:
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pubs:892613
- Deposit date:
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2020-06-23
Terms of use
- Copyright holder:
- British Pharmacological Society
- Copyright date:
- 2018
- Rights statement:
- © 2018 The British Pharmacological Society
- Notes:
- This is the accepted manuscript version of the article. The final version is available online from Wiley at https://dx.doi.org/10.1111/bph.14368
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