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The blood-brain barrier in multiple sclerosis: a target for treatment?
Published on June 28, 2018 42 min
A selection of talks on Immunology & Inflammation
Lymphocyte homing: getting lymphocytes to the right place at the right time
- Prof. Ann Ager
- Cardiff University, UK
Hello, I would like to start this Henry Stewart lecture by introducing myself. My name is Elga de Vries. I work in the MS center in Amsterdam VU Medical Center. I've been working on the blood-brain barrier for a long time, and I have a specific interest in the blood-brain barrier in multiple sclerosis. Recent insights make me wonder whether this can be a target for treatment.
So first my disclosures, just to see that, I have different grants and speaker fees. A lot of the work that I will be talking about today is funded by the foundation of MS research.
So to start off the brain endothelium, as you can see on the left-hand side, is highly vascularized and it has a very dense capillary network. On the right-hand side, when we have an enlargement of a brain capillary, you can see that in the middle, there is a capillary lumen, and that is closed (surrounded) by the endothelial cells. The endothelial cells are connected to each other by tight junction molecules, which actually seal off the endothelium, and make it a continuous layer. The endothelial cells are ensheathed by a basal lamina that is formed either by the endothelial cells or by the glial cells, and so it is called the glial basement membrane. Furthermore what you can notice in this picture on the right-hand side, is that there are pericytes that engulf the capillary network as well. Pericytes are thought to be involved in the regulation of blood flow, but also they are of high importance for the development of the blood-brain barrier in ontogeny. Furthermore what you can see is that astrocyte endfeet are completely ensheathing the brain capillaries. So continuous communication between astrocytes and endothelium makes sure that endothelial cells form a tight blood-brain barrier. But what you can see at the bottom of this figure, is that the endothelial cells will express different transporters like Glut-1, which transport glucose into the brain; but also so-called ABC transporters, which are involved in the efflux of unwanted compounds from the endothelial cells; and thereby protecting the brain. At the cell-cell contacts, we find two types of junctions. We find the adherens junction, and that is formed by the proteins VE-Cadherin and E-Cadherin; and we find tight junctions, so-called Claudin, Claudin 1, 3 and 5 have been described to be present at the junction of complexes of endothelial cells, and also Occludin.