Platelet glycoprotein Ibα is an important mediator of ischemic stroke in mice

In this study, we used transgenic mice in which the extracellular part of GPIbα is replaced by human interleukin 4-receptor (GPIbα/IL4Rα). We observed normal brain vasculature in these mice. We compared infarct size in GPIbα/IL4Rα and wild-type (WT) mice 23 hours after 1-hour transient middle cerebral artery occlusion (tMCAO). In addition, the functional outcome was evaluated using a modified Bederson score.We found a significantly smaller infarct size in GPIbα/IL4Rα mice compared to WT mice (38.0 ± 6.5 mm3 vs. 74.2 ± 8.6 mm3, p < 0.001). The decrease in infarct size was functionally relevant as indicated by a significantly better functional Bederson score in GPIbα/IL4Rα mice compared to WT animals (1.3 ± 0.4 vs. 2.7 ± 0.3, p < 0.05).Our data illustrate and further confirm the important role of platelet GPIbα in ischemic stroke, suggesting that targeted inhibition of this receptor may open new avenues in stroke treatment.Stroke is one of the leading causes of death worldwide with limited treatment options [1]. Platelets play a pivotal role in cerebral ischemia/reperfusion injury by adhering to the damaged vessel wall, leading to further platelet recruitment and thrombus formation. The glycoprotein (GP) Ib-IX-V complex is a crucial platelet receptor for initial tethering and adhesion at sites of vascular injury. This abundant complex on the platelet surface (12,500 copies per cell) consists of the leucine-rich repeat glycoproteins GPIbα, GPIbβ, GPIX and GPV in a 2:2:2:1 ratio [2]. The adhesive function of GPIb-IX-V is mainly attributed to the interaction of GPIbα with its major ligand von Willebrand factor (VWF), exposed upon vascular damage. The central role of the GPIbα-VWF interaction in mediating initial platelet adhesion is illustrated by the bleeding disorders Bernard Soulier syndrome [3] and von Willebrand disease [4], caused by deficiency of GPIb-IX-V or VWF respectively. Besides its interaction with VWF, GPIbα can also engage counter-receptors such as αMβ2 (