In acute ischaemic stroke cessation of cerebral blood flow by thromboembolic occlusions of major cerebral arteries such as the internal carotid artery and middle cerebral artery induces very early irreversible infarction at the ischaemic core. During large vessel occlusion, large areas of brain tissue surrounding the immediately evolving infarct core, the so-called penumbra, are provisionally nourished by collateral blood flow from the brain surface. However, this collateral perfusion is typically insufficient to guarantee structural integrity. Instead, macrovascular collateral flow and microvascular collateral perfusion of the penumbra collapses over time. This secondarily developing collateral failure induces further infarct progression even before a potential recanalization by therapeutic thrombectomy.

We hypothesize that platelet adhesion receptors facilitate pathological intravascular platelet-immune cell interactions, which further induce vascular dysfunction, damage the blood-brain barrier, and exert detrimental remote effects on the brain parenchyma by promoting collateral failure. The two early-stage researchers (ECR.P07.09 and ECR.P07.10) involved in this project will work closely together to elucidate the underlying mechanisms on a molecular level and explore whether targeting platelet receptors improves the outcome in acute ischaemic stroke. Both ECRs will capitalise on the transient middle cerebral artery model in combination with pharmacological tools and mouse models. ECR.P07.09 will complement this with state-of-the-art cell culture models of the blood brain barrier. ECR.P07.10 will monitor the interaction between platelets and immune cells in the ischaemic brain with the help of multiphoton microscopy.