Development and Cell Biology of the Blood-Brain Barrier

Abstract

The vertebrate vasculature displays high organotypic specialization, with the structure and function of blood vessels catering to the specific needs of each tissue. A unique feature of the central nervous system (CNS) vasculature is the blood-brain barrier (BBB). The BBB regulates substance influx and efflux to maintain a homeostatic environment for proper brain function. Here, we review the development and cell biology of the BBB, focusing on the cellular and molecular regulation of barrier formation and the maintenance of the BBB through adulthood. We summarize unique features of CNS endothelial cells and highlight recent progress in and general principles of barrier regulation. Finally, we illustrate why a mechanistic understanding of the development and maintenance of the BBB could provide novel therapeutic opportunities for CNS drug delivery.

Keywords: astrocytes; blood-brain barrier; central nervous system; endothelial cells; neurovascular unit; pericytes.

Figure 1 –. The Neurovascular Unit

(A) Schematic illustration of a cross-section through the neurovascular unit. Capillary endothelial cells (EC) forming the vessel walls are tightly wrapped by pericytes (PC). These cells are embedded in the basement membrane (BM) and are ensheathed by astrocytic endfeet (AE). (B) Schematic of the CNS endothelium highlighting the four unique properties of the BBB.

Figure 2 –. Gradual Barrier Formation in the CNS

Depiction of a coronal brain section at E14.5 and a flat-mounted retina at P7 highlighting the spatial-temporal gradient in functional barrier formation in the CNS. The blue inset illustrates features of immature, leaky CNS barriers found in dorsal brain regions and the distal retina. Green inset shows features of the mature sealed blood-CNS barriers of ventral embryonic brain and the proximal vessels of the developing retina.