The Function and Integrity of the Neurovascular Unit Rests Upon the Integration of the Vascular and Inflammatory Cell Systems

The neurovascular unit is composed of a microvascular endothelium, neuron, and glial cell elements that are in physical proximity to the endothelium. The vascular system provides oxygen, glucose, and hormones for brain cells and guides the cells to appropriately respond to the local environment. Conversely, the brain cells, especially glial cells, can regulate the function of blood vessels in response to local requirements. The disruption of the neurovascular coordination was observed in a variety of inflammation-related diseases in brain, such as infectious diseases, stroke, vascular dementia, and multiple sclerosis. Inflammatory responses resulting from infections or injury of the brain activate the endothelium and glial cells to various degrees depending on the type, titer, or strength and duration of exposure to the agents or insults. The activation of endothelial and microglial cells may be modulated by the action of cytokines or other substances secreted from these cells. In an effort to understand the pathogenesis and find rational treatments against inflammatory disorders in brain, studies have been separately carried out using either endothelial cells or microglia. Increasing evidence, however, indicates that a crosstalk between these two cell types is important for the brain inflammation. Here, we review recent advances that provide insights into the coordinated interaction between the vascular and microglial systems, including the role of the specialized endothelium in regulating the immune response that occurs within CNS, the influence of microglial cells on the properties of endothelial cells, and the effects of endothelium on the state of microglial activation.