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Titolo:
Brain drug delivery, drug metabolism, and multidrug resistance at the choroid plexus
Autore:
Ghersi-Egea, JF; Strazielle, N;
Indirizzi:
Fac Med Leannec, INSERM, U433, F-69372 Lyon 08, France Fac Med Leannec Lyon France 08 ec, INSERM, U433, F-69372 Lyon 08, France
Titolo Testata:
MICROSCOPY RESEARCH AND TECHNIQUE
fascicolo: 1, volume: 52, anno: 2001,
pagine: 83 - 88
SICI:
1059-910X(20010101)52:1<83:BDDDMA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTATHIONE-S-TRANSFERASE; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN; P-GLYCOPROTEIN; RAT-BRAIN; ENDOTHELIAL-CELLS; CYTOCHROME-P450 1A1; TRANSPORT; BARRIER; EXPRESSION;
Keywords:
blood-brain barrier; glutathione; GST; UGT; epoxide; brain delivery; neurotoxicity; CSF;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Ghersi-Egea, JF Fac Med Leannec, INSERM, U433, Rue Guillaume Paradin, F-69372 Lyon 08, France Fac Med Leannec Rue Guillaume Paradin Lyon France 08 ance
Citazione:
J.F. Ghersi-Egea e N. Strazielle, "Brain drug delivery, drug metabolism, and multidrug resistance at the choroid plexus", MICROSC RES, 52(1), 2001, pp. 83-88

Abstract

The choroid plexuses (CPs) have the capability to modulate drug delivery to the cerebrospinal fluid (CSF) and to participate in the overall cerebral biodisposition of drugs. The specific morphological properties of the choroidal epithelium and the existence of a CSF pathway for drug distribution todifferent targets in the central nervous system suggest that the CP-CSF route is more significant than previously thought for brain drug delivery. Incontrast to its role in CSF penetration of drugs, CP is also involved in brain protection in that it has the capacity to clear the CSF from numerous potentially harmful CSF-borne exogenous and endogenous organic compounds into the blood. Furthermore, CP harbors a large panel of drug-metabolizing enzymes as well as transport proteins of the multidrug resistance phenotype, which modulate the cerebral bioavailability of drugs and toxins. The use ofan in vitro model of the choroidal epithelium suitable for drug transport studies has allowed the demonstration of the choroidal epithelium acting asan effective metabolic blood-CSF barrier toward some xenobiotics, and thata vectorial, blood-facing efflux of conjugated metabolites occurs at the choroidal epithelium. This efflux involves a specific transporter with characteristics similar to those of the multidrug resistance associated protein (MRP) family members. Indeed, at least one member, MRP1, is largely expressed at the CP epithelium, and localizes at the basolateral membrane. These metabolic and transport features of the choroidal epithelium point out the CP as a major detoxification site within the brain. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/08/20 alle ore 09:06:26