Brain endothelial cells and the glio-vascular complex

Abstract

We present and discuss the role of endothelial and astroglial cells in managing the blood-brain barrier (BBB) and aspects of pathological alterations in the BBB. The impact of astrocytes, pericytes, and perivascular cells on the induction and maintenance of the gliovascular unit is largely unidentified so far. An understanding of the signaling pathways that lie between these cell types and the endothelium and that possibly are mediated by components of the basal lamina is just beginning to emerge. The metabolism for the maintenance of the endothelial barrier is intimately linked to and dependent on the microenvironment of the brain parenchyma. We report the structure and function of the endothelial cells of brain capillaries by describing structures involved in the regulation of permeability, including transporter systems, caveolae, and tight junctions. There is increasing evidence that caveolae are not only vehicles for endo- and transcytosis, but also important regulators of tight-junction-based permeability. Tight junctions separate the luminal from the abluminal membrane domains of the endothelial cell ("fence function") and control the paracellular pathway ("gate function") thus representing the most significant structure of the BBB. In addition, the extracellular matrix between astrocytes/pericytes and endothelial cells contains numerous molecules with inherent signaling properties that have to be considered if we are to improve our knowledge of the complex and closely regulated BBB.

Interendothelial Claudin-5 Expression Depends on Cerebral Endothelial Cell–Matrix Adhesion by β1-Integrins

“…Evidence to support the involvement of the cytoskeleton derives from observations of barrier permeability and actin integrity. Signaling from b 1 -integrin involves activation of the actin cytoskeleton (Wolburg et al, 2009). In addition, TJ proteins including ZO-1, occludin, and claudin-5 bind to the cytoskeleton actin.…”

Application of High-Intensity Focused Ultrasound to the Study of Mild Traumatic Brain Injury

“…In their study of traumatic brain injury induced by controlled cortical impact, Myer et al (2006) concluded that reactive astrocytes play essential protective roles, by preserving neural tissue and restricting inflammation after moderate brain injury. In the present study, a single HIFU exposure was sufficient to elicit an elevation in GFAP immunostaining in astrocytes, a characteristic neuro-immune response to blood-brain barrier cellular injury or infection (Abbott et al 2010;Chodobski et al 2011;Wolburg et al 2009). In this study, the animals were followed for only 24 h; a longer survival time is needed to establish the profile of astroglial activation.…”

Inner Blood-Retinal Barrier Transporters: Relevance to Diabetic Retinopathy

“…At the inner BRB, the retinal endothelial cells form a tightly sealed monolayer, separating the abluminal (retina side) and luminal (blood side) domains of the retinal endothelium, and prevent paracellular transport of materials across endothelial cells between the retina and circulating blood (Wolburg et al, 2009). In particular, D-mannitol, a representative nonpermeable paracellular marker, exhibits very low blood-to-retina influx permeability while D-glucose and amino acids, the substrates of membrane transporter molecules, exhibit over a 300-fold higher permeability than that of D-mannitol (Puchowicz et al, 2004;).…”