Loss of endothelial–matrix interactions in neuroinflammation affects junctional integrity of the BBB. (A) Under physiological conditions, BBB endothelial cells are anchored via β1-integrins to the ECM proteins laminin, collagen, and perlecan in the endothelial basement membrane. β1-integrin–mediated adhesive contacts contribute by not-yet-defined downstream signaling events to junctional stabilization. (B) After ischemic stroke, edema formation and BBB breakdown is associated with loss of vascular β1-integrin, probably by shedding or degradation (indicated by a question mark). Genetic or functional inactivation of β1-integrin at the BBB induces BBB leakiness by reducing the association of p120 and β-catenin with VE-cadherin. This leads to increased internalization of VE-cadherin via clathrin-coated pits and ultimately loss of junctional claudin-5. BM, basement membrane.