title: Ischaemic stroke: a thrombo-inflammatory disease?
abstract: Ischaemic stroke is a leading cause of death and disability worldwide. The complex cellular interactions leading from thromboembolic vessel occlusion to infarct development within the brain parenchyma in acute stroke are poorly understood, which translates into only one approved effective treatment, thrombolysis. Importantly, however, patients can develop progressive stroke despite reperfusion of previously occluded major intracranial arteries, a process referred to as 'reperfusion injury' which can be reproduced in the mouse model of transient middle cerebral artery occlusion (tMCAO). Although pathological platelet and coagulant activity have long been recognized to be involved in the initiation of ischaemic stroke, their contribution to infarct maturation remained elusive. Experimental evidence now suggests that early platelet adhesion/activation mechanisms involving the von Willebrand factor (vWF) receptor glycoprotein (GP) Ib, its ligand vWF, and the collagen receptor GPVI are critical pathogenic factors in infarct development following tMCAO, whereas platelet aggregation through GPIIb/IIIa is not. Further experimental work indicates that these pathways in conjunction with coagulation factor XII (FXII)-driven processes orchestrate a 'thrombo-inflammatory' cascade in acute stroke that results in infarct growth. This review summarizes these recent developments and briefly discusses their potential clinical impact.
authors.affiliation: University Hospital Würzburg, Rudolf Virchow Centre, DFG Research Centre for Experimental Biomedicine, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. bernhard.nieswandt@virchow.uni-wuerzburg.de
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.forename: Guido
authors.initials: G
authors.lastname: Stoll
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001792:Blood Platelets; D006801:Humans; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D020521:Stroke; D014841:von Willebrand Factor
chemical_list: D000911:Antibodies, Monoclonal; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor