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Neutrophil extracellular traps: a novel target in acute ischemic stroke?

Stroke is one of the leading causes of death 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. Ischemic stroke is caused by a thrombotic obstruction in one major or multiple smaller arteries impairing blood flow to the brain. This results in irreversible damage of brain tissue. 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 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. For unknown reasons, use of t-PA leads to the dissolution of occluding thrombi in some cases, but not in others, suggesting that other unknown partners may be involved in thrombus stability. In fact, it is surprising how little is known about the exact composition of thrombi that cause ischemic stroke. 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. Even though reperfusion injury is clinically very important, the underlying cellular and molecular interactions are still poorly understood. 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. The role of NETs in stroke has not been investigated to date. The general aim of this project is therefore to investigate the involvement of NETs in ischemic stroke. We will use experimental mouse models of stroke as well as clinically relevant samples obtained from stroke patients.

Date:1 Jan 2015 →  1 Sep 2017
Keywords:inflammation, neutrophil extracellular traps, acute ischemic stroke
Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences
Project type:PhD project