fig1

Figure 1. Endothelial cells and pericytes are separated by the basement membrane. Pericyte processes sheathe most of the outer side of the basement membrane. At points of contact, pericytes communicate directly with endothelial cells through the synapse-like peg-socket contacts. Astrocytic endfoot processes unsheathe the microvessel wall, which is made up of endothelial cells and pericytes. Resting microglia have a "ramified" shape. In cases of neuronal disorders that have a primary vascular origin, circulating neurotoxins may cross the BBB to reach their neuronal targets, or proinflammatory signals from the vascular cells or reduced capillary blood flow may disrupt normal synaptic transmission and trigger neuronal injury (arrow 1). Microglia recruited from the blood or within the brain and the vessel wall can sense signals from neurons (arrow 2). Activated endothelium, microglia, and astrocytes signal back to neurons, which in most cases aggravates the neuronal injury (arrow 3). In the case of a primary neuronal disorder, signals from neurons are sent to the vascular cells and microglia (arrow 2), which activate the vasculo-glial unit and contribute to the progression of the disease (arrow 3). From Zlokovic with permission^[11].