Deciphering Cellular and Acellular Barrier Dysfunction in Cerebrovascular Diseases

We are funded by the European ERA-Net NEURON funding platform.

Ischemic stroke where a brain blood vessel is transiently blocked due to a blood clot, leading to a lack of oxygen and nutrients in an area of the brain and thus death of brain tissue. Several barriers at the brain surface and around blood vessels protect the brain from harmful factors from the outside. Breakdown of brain barriers after stroke allows uncontrolled entry of damaging white blood cells and blood components and contributes to brain swelling. Stroke therapies have aimed to block entry of white blood cells into the brain, with little success in reducing stroke severity. Our approach is different - we will detail which of the brain barriers are compromised after stroke to understand how we can restore the function of the right barrier as a new stroke therapy. We have special genetically modified mouse models that allow us to see and distinguish the brain barriers and the immune cells, by using different colour-tags, in the brain of live anesthetized animals. Changes occurring at these barriers as they occur during stroke can be visualized by specialized microscopic techniques, called “intravital microscopy”. Only in this way can factors changing brain barrier properties be identified and validated in human stroke samples, ultimately, permitting translated into a new therapy.