Pericytes are multifunctional cells embedded in the basement membrane that surround endothelial cells of the microvasculature and are essential for vascular development, barrier integrity, and regulation of blood flow. In the brain, they are integral components of the neurovascular unit (NVU), where they interact with astrocytes, microglia, neurons and endothelial cells to maintain blood-brain barrier (BBB) function and cerebral perfusion.

Beyond their structural and homeostatic roles, pericytes have emerged as key modulators of immune cell trafficking during inflammation. They produce chemokines and physically guide neutrophils during transvascular migration. At the same time, platelets are increasingly recognised for their immune-modulatory function and their ability to influence vascular cell behaviour.

This project builds on recent in vivo findings from the applicants’ labs demonstrating that platelets adhere to inflamed venules, migrate across endothelial junctions, and engage in direct contact with pericytes. Platelet-derived mediators induce a pro-inflammatory phenotype and contraction in pericytes, thereby potentially influencing neutrophil extravasation and vascular leakage.

Using advanced confocal intravital microscopy (IVM) of the inflamed cremaster muscle, P06 will investigate the molecular mechanisms by which platelet adhesion receptors and secreted factors modulate pericyte function, with a particular focus on neutrophil migration and vascular permeability. In a second model, the project will assess the contribution of platelet-pericyte interactions to microvascular dysfunction and no-reflow in the ischaemic brain, in collaboration with P07.

The doctoral researcher will apply cutting-edge imaging approaches in combination with genetic mouse models, whole-mount immunostaining, and in vitro pericyte assays to uncover a previously unrecognised cellular crosstalk critical for thrombo-inflammation.

Early-stage researcher ECR.P06.08 will determine the detailed spatiotemporal dynamics of platelet interactions with endothelial cells and pericytes and their impact on neutrophil transmigration using advanced confocal intravital microscopy (IVM) on the inflamed mouse cremaster muscle as key technique. The involved molecular mechanisms will be determined using genetically modified mouse colonies and specific inhibitors in combination with microscopy and immunological methods. In addition, ECR.P06.08 will collaborate with ECR.P07.09 & ECR.P07.10 to assess whether platelet-driven pericyte contraction contributes to changes in the cerebral microvasculature and no-reflow in the ischaemic brain following ischaemic stroke. To do so, we will capitalise on the transient middle cerebral artery model of ischaemic stroke in combination with our established multiphoton IVM of the cerebral vasculature.