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.