Neutrophil Extracellular Traps, von Willebrand factor and Extracellular DNA as mediators of Ischemic Stroke Pathogenesis

Ischemic stroke, caused by an occluding thrombus which hinders cerebral blood flow, is still one of the leading causes of death and sustained disability worldwide. Nowadays, ischemic stroke management relies on the rapid removal of the occluding thrombus, thereby allowing reperfusion of the ischemic territory. Pharmacological thrombolysis or mechanical thrombectomy, which are currently the only approved strategies to recanalize the occluded cerebral artery, are still hampered by various limitations. Moreover, even after successful recanalization, ischemic stroke brain damage can still progressively increase, leading to worse patient outcomes. NETs and VWF were recently recognized as key players involved in the pathophysiology of ischemic stroke. It has become clear that NETs and VWF play an unmistakable role in both therapy resistance and in cerebral I/R injury, however, their specific contribution to these processes remains a largely unexplored topic in the field. The aim of this doctoral thesis was, therefore, to further investigate NET formation as well as to better understand the role of VWF, during ischemia and subsequent reperfusion. In addition, we aimed to unravel the contribution of exDNA, one of the major components of NETs, in ischemic stroke thrombi and its relation to ischemic stroke management. Together, our results could provide additional basic insights to aid in the development of novel therapeutic strategies, possibly by targeting NETs and VWF.