Looking at the blood–brain barrier: Molecular anatomy and possible investigation approaches

• Published in: Brain Research Reviews Vol. 64; no. 2; pp. 328 - 363
• Main Authors: Cardoso, Filipa Lourenço, Brites, Dora, Brito, Maria Alexandra
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 24.09.2010; Elsevier
• Subjects: Animals; Basement membranes; Biological and medical sciences; Blood-Brain Barrier - anatomy & histology; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - physiology; Blood–brain barrier; Brain microvascular endothelial cell; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Fundamental and applied biological sciences. Psychology; Humans; Intercellular junction; Intercellular Junctions - genetics; Intercellular Junctions - metabolism; Neuroglia - physiology; Neurology; Neurons - physiology; Neurovascular unit; Signal Transduction - genetics; Signal Transduction - physiology; Signaling; Stem-cell niche; Tight Junctions - metabolism; Transport system; Vertebrates: nervous system and sense organs; eNOS; BBB; phosphatidylinositol-3 kinase; brain microvascular endothelial cell; tumor necrosis factor-alpha; blood–brain barrier; PI3K; cyclic AMP; acquired immune deficiency syndrome; Src family of kinases; nitric oxide; IL; myosin light-chain kinase; human brain microvascular endothelial cell; Transport system; AJ; central nervous system; ZO; vascular CAM; human immunodeficiency virus; SEM; lipopolysaccharide; intercellular adhesion molecule; ABC; junctional adhesion molecule; membrane-associated guanlylate kinase; ROCK; CNS; cAMP; LPS; mitogen-activated protein kinase; myosin light-chain; MAGUK; SFK; ATP-binding cassette transporter; tight junction; neurovascular unit; Intercellular junction; MLCK; Signaling; HIV; protein tyrosine kinase; TJ; glucose transporter-1; Rho kinase; MLC; JNK; NVU; BMVEC; GLUT-1; transendothelial electrical resistance; VEGFR; endothelial nitric oxide synthase; transmission electron microscopy; EC; extracellular signal-related kinases; scanning electron microscopy; c-Jun N-terminal kinase; cell adhesion molecules; HBMVEC; P-gp; PKB; PKA; Stem-cell niche; AIDS; PKC; MAPK; PKG; CAM; VE; MMP; VCAM; ROS; NO; PTK; cGMP; adherens junction; reactive oxygen species; ERK 1/2; protein kinase G; interleukin; protein kinase A; protein kinase C; protein kinase B; ICAM; endothelial cell; VEGF; cyclic GMP; vascular endothelial; P-glycoprotein; TNF-α; vascular endothelial growth factor; JAM; matrix metalloproteinase; TEER; vascular endothelial growth factor receptor; TEM; zonula occludens; Brain microvascular endothelial cell; Neurovascular unit; Blood–brain barrier; Endothelial cell; Blood―brain barrier; Stem cell; Biological transport; Central nervous system; Review; Anatomy; Blood brain barrier; Encephalon; Microcirculation; Signal transduction
• ISSN: 0165-0173; 1872-6321
• DOI: 10.1016/j.brainresrev.2010.05.003

Abstract The blood–brain barrier (BBB) is a dynamic and complex interface between blood and the central nervous system that strictly controls the exchanges between the blood and brain compartments, therefore playing a key role in brain homeostasis and providing protection against many toxic compounds and pathogens. In this review, the unique properties of brain microvascular endothelial cells and intercellular junctions are examined. The specific interactions between endothelial cells and basement membrane as well as neighboring perivascular pericytes, glial cells and neurons, which altogether constitute the neurovascular unit and play an essential role in both health and function of the central nervous system, are also explored. Some relevant pathways across the endothelium, as well as mechanisms involved in the regulation of BBB permeability, and the emerging role of the BBB as a signaling interface are addressed as well. Furthermore, we summarize some of the experimental approaches that can be used to monitor BBB properties and function in a variety of conditions and have allowed recent advances in BBB knowledge. Elucidation of the molecular anatomy and dynamics of the BBB is an essential step for the development of new strategies directed to maintain or restore BBB integrity and barrier function and ultimately preserve the delicate interstitial brain environment.