BDNF: novel actor in hemostasis and ischemic stroke – BISTRO

Despite major advances in neurovascular research, stroke remains the second most common cause of death worldwide and a leading global cause of disability. Unravelling pathophysiological mechanisms might lead to the identification of new therapeutic targets, preventive approaches, and/or diagnostic biomarkers needed to rapidly and reliably identify patients with acute ischemic stroke, thus decreasing time to treatment and improving functional outcome. While initially discovered in neurons, recent studies show that Brain-Derived Neurotrophic Factor (BDNF) is a growth factor highly concentrated in blood platelets. Moreover, they show that exogenous BDNF activates isolated platelets in autocrine/paracrine manner while promoting fibrin clot lysis in purified system. According to our preliminary results, exogenous BDNF increases platelet adhesion to collagen and fibrinogen under arterial and venous shear stress, respectively, and enhances platelet clot retraction. It promotes thrombin generation while favoring clot lysis in plasma and decreasing clot firmness in whole blood. On the flip side, few studies show that BDNF induces oxidative stress and enhances local inflammation within atherosclerotic plaques. In the context of limited and conflicting available data, our translational research project aims at extensively investigating endogenous (i.e., circulating) BDNF in vitro effects on various platelet functions and interplay with leukocytes, coagulation, and fibrinolysis as well as in vivo in bleeding and ischemic stroke rat models and confirming our results ex vivo in a large stroke patient cohort. Our project is of utmost importance since it would confirm the emerging role of BDNF as a novel actor in hemostasis and thrombosis, thus might particularly lead to the development of novel strategies for rapid diagnosis, prevention and/or treatment of ischemic stroke and vascular cognitive impairment.