Detoxification systems, passive and specific transport for drugs at the blood-CSF barrier in normal and pathological situations.
The production by the choroid plexuses of the cerebrospinal fluid (CSF), its circulation and resorption are unique characteristics of the central nervous system (CNS). In conjunction with the blood-brain barrier, the blood-cerebrospinal fluid barrier and the flow dynamic of this fluid are the main elements setting the cerebral availability of drugs. The exchanges between the blood and the cerebrospinal fluid across the choroidal epithelium are tightly regulated, in the presence of interepithelial tight junctions, by various transport and metabolic processes. In this article, we describe the different pathways of biotransformation present at the choroid plexus for drug and toxic compounds, and review the evidence that they indeed can act as a mechanism of neuroprotection. Then, we focus on the expression of nucleoside transporters and multispecific drug transporters at the choroid plexus, and the influence of these various transport systems on the cerebral availability of pharmacologically active anti-HIV nucleoside analogs. Pharmacological strategies that can be developed to increase either brain protection or brain drug delivery at the choroid plexus will be presented. Finally, the status of drug transport in the context of CNS diseases and the consequences of their possible alteration will be discussed.
Strazielle
Nathalie
N
INSERM U433, Faculté de Médecine RTH Laennec, Rue Guillaume Paradin, 69008 Lyon, France.
Khuth
Seng T
ST
Ghersi-Egea
Jean-François
JF
D000818:Animals; D001692:Biological Transport; D001711:Biotransformation; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D033703:Nucleoside Transport Proteins / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology
D033703:Nucleoside Transport Proteins