Blood-brain interfaces and cerebral drug bioavailability

Revue neurologique
J-F Ghersi-EgeaNathalie Strazielle

Abstract

The low cerebral bioavailability of various drugs is a limiting factor in the treatment of neurological diseases. The restricted penetration of active compounds into the brain is the result of the same mechanisms that are central to the maintenance of brain extracellular fluid homeostasis, in particular from the strict control imposed on exchanges across the blood-brain interfaces. Direct drug entry into the brain parenchyma occurs across the cerebral microvessel endothelium that forms the blood-brain barrier. In addition, local drug concentration measurements and cerebral imaging have clearly shown that the choroid plexuses - the main site of the blood-cerebrospinal fluid (CSF) barrier - together with the CSF circulatory system also play a significant role in setting the cerebral bioavailability of drugs and contrast agents. The entry of water-soluble therapeutic compounds into the brain is impeded by the presence of tight junctions that seal the cerebral endothelium and the choroidal epithelium. The cerebral penetration of many of the more lipid-soluble molecules is also restricted by various classes of efflux transporters that are differently distributed among both blood-brain interfaces, and comprise either multidrug resist...Continue Reading

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Citations

Jan 23, 2014·Molecular Pharmaceutics·Kathryn BallXavier Declèves
Feb 13, 2013·Journal of Pharmacokinetics and Pharmacodynamics·Elizabeth C M de Lange
Sep 22, 2012·High Altitude Medicine & Biology·Omolara O Ogunshola, Abraham Al-Ahmad
Jan 22, 2013·Expert Opinion on Drug Metabolism & Toxicology·Vijayalakshmi Ravindranath, Henry W Strobel
Dec 8, 2010·British Journal of Pharmacology·David do C MalvarGlória E P de Souza
Feb 24, 2015·Frontiers in Neuroscience·Nathalie Strazielle, Jean-François Ghersi-Egea
Aug 21, 2020·Journal of Molecular Neuroscience : MN·D Almeida-SantosCecília R A Santos
Dec 14, 2018·Frontiers in Pharmacology·Stephanie AndradeJoana A Loureiro

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Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Jean-François Ghersi-EgeaMarie-Françoise Belin
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