After brain injury, blood-brain barrier (BBB) integrity can be compromised as a consequence of the breakdown of cell-cell interactions in the neurovascular unit, resulting in the loss of the characteristic endothelial luminal-to-abluminal structure. During the process of restoration of the BBB and vascularization, the endothelial cells are continuously reshaped, with both the luminal and abluminal membranes serving as sites of signaling. Here, we focus on the bidirectional signaling processes that are rapidly initiated between endothelial and perivascular cells and occur in certain brain diseases or in response to injury. The goal of these processes is (i) the reemergence of endothelial cell polarity, (ii) the remodeling of extracellular matrix interactions, (iii) the realignment of pericytes and astrocytic endfeet with endothelial cells, and (iv) the restitution of a well-organized and stable BBB. This abluminal membrane exemplifies how the brain vasculature responds to stressors and may represent promising targets for therapeutic interventions of brain diseases.