1166 Stroke April 2016 ischemic stroke progression. 5 Stroke injury was significantly reduced on blocking the interaction between platelet GP VI and collagen. 6 Similarly, when binding of vWF to collagen was prevented, the same protective effect was observed, 7 showing that binding of platelets to collagen, either directly via GP VI or indirectly via vWF is an important step in ischemic stroke injury. The crucial role of vWF in stroke development was further demonstrated using animals deficient for this adhesion molecule. Indeed, cerebral infarctions were significantly reduced in animals that are completely deficient in vWF. 8, 9 Both endothelial cell–derived and platelet-derived vWF mediate ischemic neurodegneration. 10 Correspondingly, mice lacking the vWF cleaving enzyme ADAMTS13 presented with worse stroke outcomes, whereas infusion of recombinant ADAMTS13 reduced stroke injury via a vWF-dependent mechanism. 8, 11, 12 Further experimental evidence for the involvement of the collagen–vWF–GP Ib axis in experimental ischemic stroke is provided by studies showing a protective effect on blocking the vWF–GP Ib interaction either by inhibitory antibodies, 6, 13 by using transgenic mice lacking the extracellular GP Ib domain on platelets, 14 or by a transgenic approach using vWF mutants unable to bind GP Ib. 7 In addition, Elvers et al15 showed that mice lacking phospholipase D1, necessary for transduction of activation signals downstream of vWF-occupied GP Ib, are also significantly protected from stroke injury after transient middle cerebral artery occlusion.