Neutrophil extracellular traps (NETs) in ischemic stroke: from basic insights to potential therapies

Stroke is one of the leading causes of death and disability worldwide. Strikingly, the paramount medical relevance of ischemic stroke is in strong contrast to the limited treatment options. Indeed, only one pharmacological strategy is currently approved for acute stroke treatment: rapid thrombolysis of the occluding thrombus using tissue plasminogen activator (t-PA). However, use of t-PA has many serious limitations, including risk of bleeding, narrow therapeutic time window and neurotoxic effects. Although timely recanalization of the occluded cerebral artery is fundamental to salvage threatened ischemic tissue, reperfusion of the ischemic territory can also seriously exacerbate tissue damage by reperfusion injury, further worsening clinical outcome.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 novel treatments avenues in stroke management.