The blood-brain barrier, which is formed by the endothelial cells that line cerebral microvessels, has an important role in maintaining a precisely regulated microenvironment for reliable neuronal signalling. At present, there is great interest in the association of brain microvessels, astrocytes and neurons to form functional 'neurovascular units', and recent studies have highlighted the importance of brain endothelial cells in this modular organization. Here, we explore specific interactions between the brain endothelium, astrocytes and neurons that may regulate blood-brain barrier function. An understanding of how these interactions are disturbed in pathological conditions could lead to the development of new protective and restorative therapies.

Astrocyte–endothelial interactions at the blood–brain barrier

Structure and function of the blood–brain barrier

Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.

Reactive Oxygen Species in Inflammation and Tissue Injury

The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders

Delivery of therapeutic proteins into tissues and across the blood-brain barrier is severely limited by the size and biochemical properties of the proteins. Here it is shown that intraperitoneal injection of the 120-kilodalton β-galactosidase protein, fused to the protein transduction domain from the human immunodeficiency virus TAT protein, results in delivery of the biologically active fusion protein to all tissues in mice, including the brain. These results open new possibilities for direct delivery of proteins into patients in the context of protein therapy, as well as for epigenetic experimentation with model organisms.

https://science.sciencemag.org/content/sci/285/5433/1569.full.pdf

In Vivo Protein Transduction: Delivery of a Biologically Active Protein into the Mouse

https://www.cell.com/trends/neurosciences/pdf/S0166-2236(00)02004-X.pdf

Molecular physiology and pathophysiology of tight junctions in the blood–brain barrier

Aims/hypothesis
Although diabetes mellitus is associated with peripheral microvascular complications and increased risk of neurological events, the mechanisms by which diabetes disrupts the blood–brain barrier (BBB) are not known. Matrix metalloproteinase (MMP) activity is increased in diabetic patients, is associated with degradation of tight junction proteins, and is a known mediator of BBB compromise. We hypothesise that diabetes leads to compromise of BBB tight junctions via stimulation of MMP activity.

/pdf/increased-blood-brain-barrier-permeability-and-altered-tight-torfvhc460.pdf

Increased blood–brain barrier permeability and altered tight junctions in experimental diabetes in the rat: Contribution of hyperglycaemia and matrix metalloproteinases

Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain barrier (BBB) were investigated. Inflammation was produced by subcutaneous injection of formalin, λ-carrageenan, or complete Freund's adjuvant (CFA) into the right hind paw. In situ perfusion and Western blot analyses were performed to assess BBB integrity after inflammatory insult. In situ brain perfusion determined that peripheral inflammation significantly increased the uptake of sucrose into the cerebral hemispheres. Capillary depletion and cerebral blood flow analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Western blot analyses showed altered tight junctional protein expression during peripheral inflammation. Occludin significantly decreased in the λ-carrageenan- and CFA-treated groups. Zonula occluden-1 expression was significantly increased in all pain models. Claudin-1 protein expression was present at the BBB and remained uncha...

/pdf/inflammatory-pain-alters-blood-brain-barrier-permeability-1gjm1rg5nv.pdf

Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression

https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(08)00023-0.pdf

Richard D. Egleton

Papers

Molecular physiology and pathophysiology of tight junctions in the blood–brain barrier

Increased blood–brain barrier permeability and altered tight junctions in experimental diabetes in the rat: Contribution of hyperglycaemia and matrix metalloproteinases

Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression

Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis

Peptide drug modifications to enhance bioavailability and blood-brain barrier permeability.