The extracellular matrix of the blood-brain barrier: structural and functional roles in health, aging, and Alzheimer's disease

Abstract

There is increasing interest in defining the location, content, and role of extracellular matrix (ECM) components in brain structure and function during development, aging, injury, and neurodegeneration. Studies in vivo confirm brain ECM has a dynamic composition with constitutive and induced alterations that impact subsequent cell-cell and cell-matrix interactions. Moreover, it is clear that for any given ECM component, the brain region, and cell type within that location, determines the direction, magnitude, and composition of those changes. This review will examine the ECM at the neurovascular unit (NVU) and the blood-brain barrier (BBB) within the NVU. The discussion will begin at the glycocalyx ECM on the luminal surface of the vasculature, and progress to the abluminal side with a focus on changes in basement membrane ECM during aging and neurodegeneration.

Keywords: Glycocalyx; aged; basement membrane; neurodegeneration.

Figure 1.

Glycocalyx of the brain vasculature. To focus on ECM, note that gap junctions, tight junctions, and regulatory molecules are not shown. Heparan sulfate proteoglycans (HSPGs), Proteoglycans (PGs), Chondroitin sulfate proteoglycans (CSPGs), Endothelial cell (EC), Hyaluronan (HA), Immunoglobulins (Ig), Red blood cells (RBC).

Figure 2.

Extracellular matrix (ECM) in the vascular and parenchymal basement membrane (BM). To focus on ECM, note that gap junctions, tight junctions, and regulatory molecules are not shown. Endothelial cell (EC), Red blood cells (RBC).