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Platelets in Acute Ischemic Stroke

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Platelets in Thrombotic and Non-Thrombotic Disorders

Abstract

Ischemic stroke and myocardial infarction are the major causes of death and disability worldwide. Rapid restoration of blood flow by pharmacological thrombolysis and/or mechanical thrombectomy is the mainstay of acute stroke treatment, but does not guarantee a favorable outcome. Reperfusion injury denotes the acute, paradoxically harmful aspect of blood flow return in the ischemic brain which involves platelet activation and, surprisingly, immune cell recruitment. In experimental stroke, glycoprotein (GP)Ibα facilitated tethering of platelets to the postischemic brain endothelium by binding to von Willebrand factor (VWF), while firm adhesion and platelet activation were mediated by GPVI signaling. Accordingly, blocking of platelet GPIbα or GPVI, as well as reducing circulating VWF, dramatically improved stroke outcome by protecting the microvasculature during reperfusion and in addition accelerated recanalization during thrombolysis. Despite interfering with platelet function, no bleeding complications occurred, in contrast to devastating intracranial hemorrhages observed after blocking platelet aggregation via αIIbβ3. It will be essential to further dissect pathological platelet functions and activation pathways involved in reperfusion injury from those indispensable as gatekeepers of hemostasis in the stroke-injured brain. The pathophysiology of acute stroke is even more complex since it involves concerted detrimental actions of platelets and T-cells, referred to as “thrombo-inflammation,” which await further elucidation.

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Acknowledgments

Work in the authors’ laboratories was supported by the Deutsche Forschungsgemeinschaft, Bonn (SFB 688 A1, A13, B1, B7). We thank our numerous colleagues who contributed to the research cited in this article: Deya Cherpokova for preparing Fig. 3, Dr. Michael Schuhmann for Fig. 2F, and Prof. Dr. Làszló Solymosi, Head of the Department of Neuroradiology, University Hospital of Würzburg, for providing CT scans and angiograms of stroke patients.

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Authors and Affiliations

  1. Department of Neurology, University Hospital Würzburg, 97080, Würzburg, Germany

    Guido Stoll

  2. Department of Neurology, University Hospital Essen, 45147, Essen, Germany

    Christoph Kleinschnitz

  3. Institute of Experimental Biomedicine and Rudolf-Virchow Center, University Hospital Würzburg, 97080, Würzburg, Germany

    Bernhard Nieswandt

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  1. Guido Stoll
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  2. Christoph Kleinschnitz
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  3. Bernhard Nieswandt
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Correspondence to Guido Stoll .

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Editors and Affiliations

  1. Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia , Perugia, Italy

    Paolo Gresele

  2. Houston Methodist Hospital , Houston, Texas, USA

    Neal S. Kleiman

  3. Bloodworks Northwest, University of Washington , Seattle, Washington, USA

    José A. Lopez

  4. Sackler Inst of Pulmonary Pharmacol, King’s College London, London, United Kingdom

    Clive P. Page

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Stoll, G., Kleinschnitz, C., Nieswandt, B. (2017). Platelets in Acute Ischemic Stroke. In: Gresele, P., Kleiman, N., Lopez, J., Page, C. (eds) Platelets in Thrombotic and Non-Thrombotic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-47462-5_68

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