title: Blocking of platelet glycoprotein receptor Ib reduces "thrombo-inflammation" in mice with acute ischemic stroke.
abstract: Ischemic stroke causes a strong inflammatory response that includes T cells, monocytes/macrophages, and neutrophils. Interaction of these immune cells with platelets and endothelial cells facilitates microvascular dysfunction and leads to secondary infarct growth. We recently showed that blocking of platelet glycoprotein (GP) receptor Ib improves stroke outcome without increasing the risk of intracerebral hemorrhage. Until now, it has been unclear whether GPIb only mediates thrombus formation or also contributes to the pathophysiology of local inflammation.
  
  
  
  Focal cerebral ischemia was induced in C57BL/6 mice by a 60-min transient middle cerebral artery occlusion (tMCAO). Animals were treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab). Rat immunoglobulin G (IgG) Fab was used as control treatment. Stroke outcome, including infarct size and functional deficits as well as the local inflammatory response, was assessed on day 1 after tMCAO.
  
  
  
  Blocking of GPIb reduced stroke size and improved functional outcome on day 1 after tMCAO without increasing the risk of intracerebral hemorrhage. As expected, disruption of GPIb-mediated pathways in platelets significantly reduced thrombus burden in the cerebral microvasculature. In addition, inhibition of GPIb limited the local inflammatory response in the ischemic brain as indicated by lower numbers of infiltrating T cells and macrophages and lower expression levels of inflammatory cytokines compared with rat IgG Fab-treated controls.
  
  
  
  In acute ischemic stroke, thrombus formation and inflammation are closely intertwined ("thrombo-inflammation"). Blocking of platelet GPIb can ameliorate thrombo-inflammation.
authors.affiliation: Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080, Würzburg, Germany.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schuhmann
authors.affiliation: Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080, Würzburg, Germany.
authors.forename: Josua
authors.initials: J
authors.lastname: Guthmann
authors.affiliation: Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080, Würzburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Stoll
authors.affiliation: Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080, Würzburg, Germany. Kraft_P1@ukw.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080, Würzburg, Germany. christoph.kleinschnitz@uk-essen.de.|Department of Neurology, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany. christoph.kleinschnitz@uk-essen.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
mesh_terms: D000818:Animals; D007249:Inflammation / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism / Q000473:pathology*; D013927:Thrombosis / Q000473:pathology
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex
keywords: Glycoprotein receptor Ib; Ischemic stroke; Thrombo-inflammation; Transient middle cerebral artery occlusion