Tight junctions of the blood-brain barrier

Multicellular organisms are primarily required to establish a distinct internal environment to maintain homeostasis. As a result, all internal and external surfaces of organs, such as skin, stomach, and intestines, are covered with various kinds of epithelia. In order to work efficiently as a barrier, intercellular spaces of these epithelial sheets are strictly sealed by junctional complexes. Likewise, microvascular-associated brain endothelial cells are linked by intercellular junctions. The main structures responsible for the barrier properties are tight junctions (1,2). These intercellular structures are located at the most apical section of the plasma membrane of adjacent cells (Fig. 1A), whereas adherens junctions are found in the basal part of the cell membrane. Tight junctions also act as an intramembrane fence that prevents the intermixing of apical and basolateral lipids in the exocytoplasmic leafiet of the plasma membrane. Points of cell-cell contact are sites where integral proteins of two adjacent membranes meet within the cellular space (Fig. 1B). The adjoining membranes make contact at intermittent points, rather than being fused over a large surface area. The integrity/permeability of tight junctions can be assessed by transendothelial electric resistance (TEER) measurements. In this chapter we describe the molecular composition of tight junctions and their role in several intercellular signaling pathways and leukocyte migration.