Platelets and Stroke

Ischemic stroke is the third most common cause of disability worldwide. Since ischemic stroke results from an occlusion of a brain-supplying artery, rapid recanalization either by intravenous thrombolysis or by endovascular thrombectomy is the primary clinical objective. Following restoration of blood flow, reperfusion injury often occurs encompassing a large number of detrimental biochemical processes. Based on animal models of stroke, tethering of platelets on endothelial cells is mediated by the glycoprotein (GP) Ib–V–IX receptor complex on the surface of platelets. This complex facilitates the binding of von Willebrand factor (vWF) to the damaged sub-endothelium and thus the first critical step in platelet adhesion. Further glycoprotein receptors, i.e., glycoprotein (PG) VI, and GPIIb/IIIa are also involved in aggregation and adhesion of platelets. Aggregates of adherent, activated platelets express adhesive molecules, namely, P-selectin, which binds to P-selectin glycoprotein ligand-1 (PSGL-1), the main receptor for P-selectin on leukocytes. Adherence of leukocytes and the subsequent release of pro-inflammatory factors are particular mechanisms that show how platelets induce inflammatory processes. Platelets are also connected in further ways to cellular and humoral components of the immune system, such as T cells, macrophages, and the complement system. This has led us to develop the term “thrombo-inflammation.” Both thrombotic and inflammatory mechanisms are highly intertwined in the pathophysiology of ischemic stroke. Thrombus formation and inflammation are therefore promising targets for the development of novel therapeutic strategies. The growing insights into thrombo-inflammation after cerebral ischemia might provide a platform for further exploration of the critical interface between inflammation and thrombosis after ischemic stroke. These interesting findings in the field of cerebral thrombo-inflammation should encourage stroke researchers to seek further treatments that target the reduction of thrombo-inflammation in stroke and other cardiovascular diseases.