Blood Brain Barrier Analysis

1.1 Blood-Brain Barrier

The Blood-Brain Barrier (BBB) is described as a dynamic interface between the peripheral circulation and the central nervous system. It functions as a physical and metabolical barrier between the nervous system and the circulating blood and is important for neuronal microenvironment, protection against in the peripheral blood circulating toxic molecules and to prevent neurotransmitters to escape into the general circulation. The barrier function was first discovered in 1913 by Goldman and colleagues. They injected colored dye into the blood stream of dogs and observed an absence of dye specifically in the central nervous system (Goncalves et al., 2013; Liddelow, 2011). It is comprised out of the neurovascular unit, which

Already the name (derived from the Latin word ‘claudere’ meaning ‘close’) explains the function of these molecules: they join endothelial cells together and restrict movement of ions and proteins in-between cells of different tissues.

Claudins are 20-34 Kilodalton (kDa) integral membrane proteins of the tight junctions regulating its function (Goncalves et al., 2013). They consist of four-transmembrane domains, N- and C-terminal cytoplasmic domain and two extracellular loops (ECL). The majority is found in epithelial or endothelial cells of all tissues containing tight junctions (Fig. 1 B).

Several overexpression, knockdown or knockout experiments of Claudins in primary human foreskin keratinocytes, in primary rat alveolar epithelial cells and in mice show major evidence that these proteins are responsible for changes in the paracellular permeability in the brain endothelial cells (De Benedetto et al., 2011; Furuse et al., 2002; Muto et al., 2010; F. Wang et al., 2003; Watson et al., 2007). As they play part in both, the paracellular barrier and pore formation, their involvement in permeability of epithelial and endothelial cells seems to be crucial (Shen et al., 2011). Expression of these molecules however depends on the tissue and developmental stage of the