Platelets as Modulators of Cerebral Ischemia/Reperfusion Injury

Front Immunol. 2019 Nov 1:10:2505. doi: 10.3389/fimmu.2019.02505. eCollection 2019.

Abstract

Ischemic stroke is among the leading causes of disability and death worldwide. In acute ischemic stroke, the rapid recanalization of occluded cranial vessels is the primary therapeutic aim. However, experimental data (obtained using mostly the transient middle cerebral artery occlusion model) indicates that progressive stroke can still develop despite successful recanalization, a process termed "reperfusion injury." Mounting experimental evidence suggests that platelets and T cells contribute to cerebral ischemia/reperfusion injury, and ischemic stroke is increasingly considered a thrombo-inflammatory disease. The interaction of von Willebrand factor and its receptor on the platelet surface, glycoprotein Ib, as well as many activatory platelet receptors and platelet degranulation contribute to secondary infarct growth in this setting. In contrast, interference with GPIIb/IIIa-dependent platelet aggregation and thrombus formation does not improve the outcome of acute brain ischemia but dramatically increases the susceptibility to intracranial hemorrhage. Here, we summarize the current understanding of the mechanisms and the potential translational impact of platelet contributions to cerebral ischemia/reperfusion injury.

Keywords: glycoprotein Ibα; ischemic stroke; platelet; platelet degranulation; thrombo-inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Platelets*
  • Brain Ischemia*
  • Humans
  • Platelet Membrane Glycoproteins
  • Receptors, Purinergic P2
  • Receptors, Thrombin
  • Reperfusion Injury*
  • von Willebrand Factor

Substances

  • Platelet Membrane Glycoproteins
  • Receptors, Purinergic P2
  • Receptors, Thrombin
  • von Willebrand Factor