Blood-Brain Barrier Permeability: From Bench to Bedside (original) (raw)

2011, Management of Epilepsy - Research, Results and Treatment

The concept of the blood-brain barrier (termed hematoencephalic barrier) was first introduced by Lina Stern in 1921, although the early work by Paul Ehrlich and Edwin Goldmann suggested the compartmentalization between blood and brain and a role of blood vessels in maintaining these compartments (Ehrlich, 1885; Goldmann, 1913; Vein, 2008). However, actual proof of the existence of a BBB came in the 1960s. Since then, significant progress has been made in defining the functions and properties of that barrier. The BBB is a highly specialized structural and biochemical barrier that regulates the entry of blood-borne molecules and cells into brain and preserves ionic homeostasis within the brain microenvironment (Pardridge, 2007; Rubin & Staddon, 1999; Ueno, 2007). Formed at the interface between blood and brain parenchyma, the BBB is composed of a tightly sealed monolayer of brain endothelial cells at the brain capillary surface and adjacent perivascular cells, including astrocytes and pericytes. Both astrocytic endfeet and pericyte processes wrap the abluminal capillary surface and through indirect or direct synapse-like "pegsocket" interactions provide physical support and stability to the BBB (Abbott, 2002; Armulik et al, 2010; Kim et al, 2006; Williams et al, 2001). In recent years, the concept of a BBB has been significantly extended to the concept of a neurovascular unit, which best describes the dynamic communication between brain endothelium, neurons, astrocytes, pericytes, vascular smooth muscle cells, microglia and perivascular macrophages at the interface between the blood and brain parenchyma compartments (Hawkins & Davis, 2005; Wolburg et al, 2009). A healthy brain relies on all of the cells of the neurovascular unit to function properly and communicate with each other in order for neuronal synapses and circuitries to maintain normal cognitive functions (Fig. 1). 2. Blood-brain barrier junctional complexes The structural properties of the BBB are primarily determined by the endothelial junctional complexes, consisting of tight junctions (TJ) and adherens junctions (AdJ). The interactions between brain endothelial cells provide high endothelial electrical resistance barrier, in the range of 1500-2000 Ω.cm 2 (pial vessels), as compared to 3-33 Ω.cm 2 endothelial barrier in www.intechopen.com