Periodic Reporting for period 1 - PANDORA (Platelets: at the nexus of brain aneurysm)
Reporting period: 2016-12-01 to 2018-11-30
In parallel to the in vitro studies, we set up the in vivo model of intracranial aneurysm. For this purpose, I collaborated with Cyrille Orset at INSERM 919, University of Caen, France. I went to learn the model and implemented in my lab. It’s a finicky preclinical in-vivo animal model described by Nuki et al, analog to the clinical manifestation of the disease process. We implanted mice angiotensin pump to induce hypertension and then injected elastase into the cerebrospinal fluid are combined to induce intracranial aneurysm formation and rupture in mice monitored by MRI surgery. This model requires a lot of training and high skill level in microsurgery. Now, I am pretty confident with this model to further delineate the platelet mechanisms. Aside the learning curve of this model, I observed by immunohistology a thrombus in the aneurysmal sac highly enriched in platelets and leukocytes suggesting that platelets can play an instrumental role in this disease. I presented these results at seminars and open doors days in our laboratory. I also communicate this data through the class I am teaching at the University of Paris Diderot and at meetings (International Vascular Biology Meeting in Boston, European Congress on Hemostasis and Thrombosis in Den Hague and in Marseille 2018).
The ultimate goal of biomedical research is to develop novel and better therapeutic approaches for the treatment of human diseases. Importantly, cost of vascular brain diseases is considerably increasing as the population aged. This situation urges the need for new therapeutic strategy as the management of these patients is resource-intensive and has significant implications on public health, health budgets, and the education of future health professionals. Taking this into account, the overall aim of the project is to ease the social burden of an intracranial aneurysm by providing a framework for developing novel strategies and identify new therapeutic targets. We are certain that the potential clinical applications of the knowledge generated within this project are in line with the continuous effort of the European scientific community to be at the forefront of translational medicine.