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Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier

The blood-brain barrier (BBB) is a highly specialized structural and biochemical barrier that regulates the entry of blood-borne molecules into brain, and preserves ionic homeostasis within the brain microenvironment. BBB properties are primarily determined by junctional complexes between the cerebr...

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Detalles Bibliográficos
Autores principales: Stamatovic, Svetlana M, Keep, Richard F, Andjelkovic, Anuska V
Formato: Texto
Lenguaje:English
Publicado: Bentham Science Publishers Ltd. 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687937/
https://www.ncbi.nlm.nih.gov/pubmed/19506719
http://dx.doi.org/10.2174/157015908785777210
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author Stamatovic, Svetlana M
Keep, Richard F
Andjelkovic, Anuska V
author_facet Stamatovic, Svetlana M
Keep, Richard F
Andjelkovic, Anuska V
author_sort Stamatovic, Svetlana M
collection PubMed
description The blood-brain barrier (BBB) is a highly specialized structural and biochemical barrier that regulates the entry of blood-borne molecules into brain, and preserves ionic homeostasis within the brain microenvironment. BBB properties are primarily determined by junctional complexes between the cerebral endothelial cells. These complexes are comprised of tight and adherens junctions. Such restrictive angioarchitecture at the BBB reduces paracellular diffusion, while minimal vesicle transport activity in brain endothelial cells limits transcellular transport. Under normal conditions, this largely prevents the extravasation of large and small solutes (unless specific transporters are present) and prevents migration of any type of blood-borne cell. However, this is changed in many pathological conditions. There, BBB disruption (“opening”) can lead to increased paracellular permeability, allowing entry of leukocytes into brain tissue, but also contributing to edema formation. In parallel, there are changes in the endothelial pinocytotic vesicular system resulting in the uptake and transfer of fluid and macromolecules into brain parenchyma. This review highlights the route and possible factors involved in BBB disruption in a variety of neuropathological disorders (e.g. CNS inflammation, Alzheimer’s disease, Parkinson’s disease, epilepsy). It also summarizes proposed signal transduction pathways that may be involved in BBB “opening”.
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spelling pubmed-26879372009-06-08 Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier Stamatovic, Svetlana M Keep, Richard F Andjelkovic, Anuska V Curr Neuropharmacol Article The blood-brain barrier (BBB) is a highly specialized structural and biochemical barrier that regulates the entry of blood-borne molecules into brain, and preserves ionic homeostasis within the brain microenvironment. BBB properties are primarily determined by junctional complexes between the cerebral endothelial cells. These complexes are comprised of tight and adherens junctions. Such restrictive angioarchitecture at the BBB reduces paracellular diffusion, while minimal vesicle transport activity in brain endothelial cells limits transcellular transport. Under normal conditions, this largely prevents the extravasation of large and small solutes (unless specific transporters are present) and prevents migration of any type of blood-borne cell. However, this is changed in many pathological conditions. There, BBB disruption (“opening”) can lead to increased paracellular permeability, allowing entry of leukocytes into brain tissue, but also contributing to edema formation. In parallel, there are changes in the endothelial pinocytotic vesicular system resulting in the uptake and transfer of fluid and macromolecules into brain parenchyma. This review highlights the route and possible factors involved in BBB disruption in a variety of neuropathological disorders (e.g. CNS inflammation, Alzheimer’s disease, Parkinson’s disease, epilepsy). It also summarizes proposed signal transduction pathways that may be involved in BBB “opening”. Bentham Science Publishers Ltd. 2008-09 /pmc/articles/PMC2687937/ /pubmed/19506719 http://dx.doi.org/10.2174/157015908785777210 Text en ©2008 Bentham Science Publishers Ltd. http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/) which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Stamatovic, Svetlana M
Keep, Richard F
Andjelkovic, Anuska V
Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier
title Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier
title_full Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier
title_fullStr Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier
title_full_unstemmed Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier
title_short Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier
title_sort brain endothelial cell-cell junctions: how to “open” the blood brain barrier
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687937/
https://www.ncbi.nlm.nih.gov/pubmed/19506719
http://dx.doi.org/10.2174/157015908785777210
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