Aging and the neurovascular unit

Abstract

With the demonstration that acute recanalization of obstructed symptomatic cerebral arteries during ischemic stroke can result in substantial improvement in clinical outcome, the variability in clinical responses, and in hemorrhagic transformation, requires attention. This short review addresses the effect of aging and amyloid deposition disease on microvessel integrity, interactions within the neurovascular unit, cerebral tissue susceptibility to ischemic injury, and postischemic inflammation, and ultimately on the outcomes and safety of acute recanalization during ischemic stroke. Microvessels and neighboring neurons respond simultaneously to focal ischemia. The cellular components and matrix barriers of the neurovascular unit all respond to ischemia; however, their coordinate interactions are not understood. Furthermore, there is little known about the cell-cell and cell-matrix interactions within the unit, or about the effect of β-amyloid on microvessel responses during ischemia. These considerations indicate the need for a coordinated research effort to understand the origins of the variability in recanalization outcome.

Figure 1

Comparison of the general changes in the expressions of recognized matrix adhesion receptors and matrix protein substrates in cerebral microvessels (capillary and larger microvessels) subject to focal ischemia (middle cerebral artery occlusion [MCA:O] in the nonhuman primate and murine cells in culture) or subject to amyloid deposition (in humans) (see the text for references). N = no change; arrows = decreased expression or loss of antigen.