Injury and repair in the neurovascular unit

Abstract

The neurovascular unit provides a conceptual framework for investigating the pathophysiology of how brain cells die after stroke, brain injury, and neurodegeneration. Emerging data now suggest that this concept can be further extended. Cell-cell signaling between neuronal, glial, and vascular elements in the brain not only mediates the mechanisms of acute injury, but integrated responses in these same elements may also be required for recovery as the entire neurovascular unit attempts to reorganize and remodel. Understanding the common signals and substrates of this transition between acute injury and delayed repair in the neurovascular unit may reveal useful paradigms for augmenting neuronal, glial, and vascular plasticity in damaged and diseased brain.

Figure 1

Schematic of the multicellular interactions that mediate the transition from injury into repair in the neurovascular unit. During injury and disease, the BBB is leaky, inflammation is damaging, and neurotoxicity predominates. But during repair, endogenous mechanisms are activated that involve angiogenesis and neurogenesis, trophic glial reactions, and recruitment of beneficial aspects of inflammation and remodeling. In this simplified schematic, we only depict neurons, astrocytes, microglia and endothelium. Of course, recovery after CNS injury will also involve many other cell types including pericytes, smooth muscle cells, oligodendrocytes, infiltrating or resident immune cells as well as systemic responses in other organs. Ultimately, cell–cell signaling between all elements of the neurovascular unit is required to support neural plasticity and functional compensation and recovery.