Poster Elodie Laridan onderzoeksdag 2015

Geneeskunde
Neutrophil extracellular traps: a novel target in acute ischemic stroke?
Elodie Laridan
Promotor: Prof. Dr. Ir. Simon De Meyer
Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
INTRODUCTION
WHY ARE NEUTROPHIL EXTRACELLULAR TRAPS SO IMPORTANT?
Ischemic stroke is one of the major causes of death sustained disability worldwide. It results from a blood clot
impairing blood flow to the brain causing irreversible tissue damage (ischemia).
Unfortunately, the use of tissue plasminogen activator (t-PA) as
only therapeutic has many limitations and fails to dissolve blood
clots in some cases. This suggests that other unknown factors
may be involved in clot stability. In addition, reperfusion of
damaged brain tissue leads to additional tissue injury caused by a
complex interplay of inflammation and blood clotting
(thrombosis).
Neutrophil extracellular traps (NETs) are a new link between
thrombosis and inflammation. NETs are formed when neutrophils
expulse their DNA forming a net with immunological properties.
They can also promote blood clot formation by attracting platelets
(see figure below) and potentially form a support for blood clot
formation and stabilization. NET markers in blood have been
shown to reflect disease activity in several clotting diseases, but
little is known about their role in stroke.
Remove blood clot
Time lost = brain lost
Ischemic stroke
Therapy fails in some cases:
WHY?
Defense against bacteria
NETs
• Blood clot formation
• Blood vessel and
brain tissue damage
Do NETs support blood clot formation explaining in part why therapy fails?
Do NETs further contribute to stroke progression?
HOW TO INVESTIGATE?
NET formation in damaged (ischemic) brain area following stroke?
•
Mouse model of ischemia/reperfusion
•
Detection of NETs with antibodies
DNase1 as NETs degrading enzyme: ability to help dissolve blood clots?
•
In vitro testing
•
Mouse model of cerebral blood clot formation
Biomarkers for NETs in plasma from acute stroke patients?
Detection of typical NETs markers
NETs in human blood clots from acute stroke patients?
Searching for NETs in blood clots using antibodies
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