Low Flow and Microvascular Shunts: A Final Common Pathway to Cerebrovascular Disease: A Working Hypothesis

Abstract

Low flow and microvascular shunts (MVS) is the final common pathway in cerebrovascular disease. Low flow in brain capillaries (diam. 3–8 μm) decreases endothelial wall shear rate sensed by the glycocalyx regulating endothelial function: water permeability; nitric oxide synthesis via nitric oxide synthase; leucocyte adhesion to the endothelial wall and penetration into the tissue; activation of cytokines and chemokines initiating inflammation in tissue. Tissue edema combined with pericyte and astrocyte capillary constriction increases capillary resistance. Increased capillary resistance diverts flow through MVS (diam. 10–25 μm) that are non-nutritive, without gas exchange, waste or metabolite clearance and cerebral blood flow (CBF) regulation. MVS predominate in subcortical and periventricular white matter. The shift in flow from capillaries to MVS is a pathological, maladaptive process. Low perfusion in the injured tissue exacerbates brain edema. Low blood flow and MVS alone can lead to all of the processes involved in tissue injury including inflammation and microglial activation.