Microvessel remodeling in cerebral ischemia

The neurovascular (NV) unit, broadly defined as a segment of brain vasculature, is composed of functionally integrated cellular (including brain endothelial cells, astrocytes, pericytes, and smooth muscle cells) and acellular elements that form the basement membrane. Brain insults or conditions characterized by tissue hypoxia induce dramatic changes in the NV unit that include the disruption of interendothelial tight junctions, breakdown of the basal lamina, and endothelial proliferation, migration, and reorganization to form new capillaries and microvessels. This NV remodeling is controlled by a complex interplay of numerous mediators originating from cellular components of the NV unit and from breakdown of the extracellular matrix. Several of these mediator families are also involved in neuronal remodeling, thus providing for integration of vascular and neuronal responses to the ischemic state. On the global molecular scale, changes in ischemic cerebral microvessels include temporally controlled regulation of genes and proteins involved in cell cycle, blood-brain barrier phenotypic properties, cell proliferation, motility, and inflammation. The integration/coordination of angiogenic and neuronal remodeling during postischemic brain recovery is an important determinant of the overall neurological outcome.NRC publication: Ye