Periodic Reporting for period 3 - Damocles (Modelling brain aneurysm to elucidate the role of platelets)
Berichtszeitraum: 2021-06-01 bis 2022-11-30
- Aim 1 will investigate platelet activation status in peripheral blood and within the aneurysmal sac from patients with unruptured IA.
- Aim 2 will decipher platelet mechanisms and responses in artificial aneurysm-like vessels.
- Aim3 will evaluate platelet mechanisms in in-vivo intracranial aneurysm mouse model and test anti-platelet therapies with the ultimate goal of generating targeted therapies that result in the stabilization or regression of intracranial aneurysm
Aim 1: To test the platelet activation status in patients with IA, we recruited over 70 patients with IA. Blood was drawn within or upstream of the aneurysm sac and in the peripheral blood. We measured several specific platelet activation markers by flow cytometry and ELISA (P-selectin exposure, integrin activation, soluble PF4). We observed that platelets from patients with IA are in a pre-activated state in the peripheral blood and in the aneurysm sac.
Aim2: To study the impact of the aneurysm geometry on platelet activation, we have access thanks to a collaboration with Dr. Boujeltia-Zouaoui at the University of Brussels, microfluidic chambers that mimic the aneurysm sac. We perfused whole blood through this chamber at a high shear rate and observed that platelet are more activated in the aneurysm sac.
Aim3: To investigate the role of platelets in an-vivo models of brain aneurysm, we had to develop 2 reliable mouse models of aneurysm: one for aneurysm formation and one for aneurysm rupture. In the rupture model, we observed mice that lack platelets develop more aneurysm rupture than mice with normal platelet count suggesting that platelets are necessary to prevent the rupture.
Our data obtained during this first midterm period suggest that platelets have an ambivalent role in brain aneurysm disease: they prevent the rupture but, platelet activation can also contribute to the aneurysm evolution.
We expect until the end of the project to tease apart which platelet mechanisms contribute to the aneurysm formation and rupture.