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Mechanisms of the Penetration of Blood-Borne Substances into the Brain

The blood-brain barrier (BBB) impedes the influx of intravascular compounds from the blood to the brain. Few blood-borne macromolecules are transferred into the brain because vesicular transcytosis in the endothelial cells is considerably limited and the tight junction is located between the endothe...

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Autor principal: Ueno, Masaki
Formato: Texto
Lenguaje:English
Publicado: Bentham Science Publishers Ltd 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730006/
https://www.ncbi.nlm.nih.gov/pubmed/19949573
http://dx.doi.org/10.2174/157015909788848901
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author Ueno, Masaki
author_facet Ueno, Masaki
author_sort Ueno, Masaki
collection PubMed
description The blood-brain barrier (BBB) impedes the influx of intravascular compounds from the blood to the brain. Few blood-borne macromolecules are transferred into the brain because vesicular transcytosis in the endothelial cells is considerably limited and the tight junction is located between the endothelial cells. At the first line of the BBB, the endothelial glycocalyx which is a negatively charged, surface coat of proteoglycans, and adsorbed plasma proteins, contributes to the vasculoprotective effects of the vessels wall and are involved in maintaining vascular permeability. In the endothelial cytoplasm of cerebral capillaries, there is an asymmetrical array of metabolic enzymes such as alkaline phosphatase, acid phosphatase, 5’-nucleotidase, adenosine triphosphatase, and nucleoside diphosphatase and these enzymes contribute to inactivation of substrates. In addition, there are several types of influx or efflux transporters at the BBB, such as P-glycoprotein (P-gp), multidrug resistance associated protein, breast cancer resistance protein, organic anion transporters, organic cation transporters, organic cation transporter novel type transporters, and monocarboxylic acid transporters. P-gp, energy-dependent efflux transporter protein, is instrumental to the barrier function. Several findings recently reported indicate that endothelial P-gp contributes to efflux of undesirable substances such as β-amyloid protein from the brain or periarterial interstitial fluid, while P-gp likely plays a crucial role in the genesis of multiple vascular abnormalities that accompany hypertension. In this review, influx and efflux mechanisms of drugs at the BBB are also reviewed and how medicines pass the BBB to reach the brain parenchyma is discussed.
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spelling pubmed-27300062009-12-01 Mechanisms of the Penetration of Blood-Borne Substances into the Brain Ueno, Masaki Curr Neuropharmacol Article The blood-brain barrier (BBB) impedes the influx of intravascular compounds from the blood to the brain. Few blood-borne macromolecules are transferred into the brain because vesicular transcytosis in the endothelial cells is considerably limited and the tight junction is located between the endothelial cells. At the first line of the BBB, the endothelial glycocalyx which is a negatively charged, surface coat of proteoglycans, and adsorbed plasma proteins, contributes to the vasculoprotective effects of the vessels wall and are involved in maintaining vascular permeability. In the endothelial cytoplasm of cerebral capillaries, there is an asymmetrical array of metabolic enzymes such as alkaline phosphatase, acid phosphatase, 5’-nucleotidase, adenosine triphosphatase, and nucleoside diphosphatase and these enzymes contribute to inactivation of substrates. In addition, there are several types of influx or efflux transporters at the BBB, such as P-glycoprotein (P-gp), multidrug resistance associated protein, breast cancer resistance protein, organic anion transporters, organic cation transporters, organic cation transporter novel type transporters, and monocarboxylic acid transporters. P-gp, energy-dependent efflux transporter protein, is instrumental to the barrier function. Several findings recently reported indicate that endothelial P-gp contributes to efflux of undesirable substances such as β-amyloid protein from the brain or periarterial interstitial fluid, while P-gp likely plays a crucial role in the genesis of multiple vascular abnormalities that accompany hypertension. In this review, influx and efflux mechanisms of drugs at the BBB are also reviewed and how medicines pass the BBB to reach the brain parenchyma is discussed. Bentham Science Publishers Ltd 2009-06 /pmc/articles/PMC2730006/ /pubmed/19949573 http://dx.doi.org/10.2174/157015909788848901 Text en ©2009 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
Ueno, Masaki
Mechanisms of the Penetration of Blood-Borne Substances into the Brain
title Mechanisms of the Penetration of Blood-Borne Substances into the Brain
title_full Mechanisms of the Penetration of Blood-Borne Substances into the Brain
title_fullStr Mechanisms of the Penetration of Blood-Borne Substances into the Brain
title_full_unstemmed Mechanisms of the Penetration of Blood-Borne Substances into the Brain
title_short Mechanisms of the Penetration of Blood-Borne Substances into the Brain
title_sort mechanisms of the penetration of blood-borne substances into the brain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730006/
https://www.ncbi.nlm.nih.gov/pubmed/19949573
http://dx.doi.org/10.2174/157015909788848901
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