Neutrophil extracellular traps: a novel thrombo-inflammatory mediator of stroke pathology?

Stroke is one of the leading causes of death and sustained disability worldwide. Despite ongoing advances in stroke imaging and treatment, ischemic and hemorrhagic stroke continue to debilitate patients with devastating outcomes at both the personal and societal levels. Strikingly, the paramount medical relevance of ischemic stroke is in strong contrast to the limited treatment options that are currently available in the stroke clinic. Indeed, only one therapeutic treatment option is currently approved: rapid thrombolysis of the occluding thrombus using tissueplasminogen activator (t-PA). However, use of t-PA has many serious limitations, including risk of bleeding, narrow therapeutic time window and neurotoxic effects. The development of novel therapies is hampered by our incomplete understanding of the complex cellular and molecular interactions underlying stroke pathology. The “thrombo-inflammatory” nature of stroke, involving a complex interplay between both thrombotic and inflammatory processes, has been widely accepted. An intriguing new link between thrombosis and inflammation has just recently been discovered: neutrophil extracellular traps or NETs. A growing body of evidence reveals that NETs also form in human thrombosis and that NET biomarkers in plasma reflect disease activity. In this project, our aim is to investigate the involvement of NETs in ischemic stroke as this could open up interesting novel treatment strategies in stroke management.