Permeability of the Blood-Brain Barrier to the Immunosuppressive Cyclic Peptide Cyclosporin A

Autor: Christopher C.W. Hughes, John Greenwood, David J. Begley, D. M. Mitrovic, Linda K. Squires, Patricia A. Revest, Berislav V. Zlokovic
Rok vydání: 1990
Předmět:
Zdroj: Journal of Neurochemistry. 55:1222-1230
ISSN: 1471-4159
0022-3042
DOI: 10.1111/j.1471-4159.1990.tb03128.x
Popis: Uptake of the immunosuppressive lipophilic peptide cyclosporin A has been measured by a number of techniques. The brain uptake index (BUI) technique in the rat yields only a small BUI value that is not significantly different from that of sucrose and mannitol and is comparable to other published BUI values for this compound. Brain perfusion studies in the guinea pig produce a unidirectional cerebrovascular permeability constant (Kin) of 1.2 +/- 0.28 microliter g-1 min-1 for the hippocampus. Intravenous bolus injection techniques also in the guinea pig characteristically produce a larger Kin value of 2.53 +/- 0.38 microliter g-1 min-1 for the same brain region, even after a correction for the inulin space of the tissue has been made. Apparent penetration of cyclosporin A into the cerebrospinal fluid (CSF) determined with the intravenous bolus injection technique is small with a Kin of 0.79 +/- 0.07 microliter g-1 min-1. However it is suggested that the radioactivity present in CSF is largely tritiated water. Studies with cultured cerebral endothelial cells from the rat have also been carried out and show that the cultured cells take up and accumulate cyclosporin A in vitro, achieving a tissue-to-medium ratio of 20 after 25 min of incubation. It is suggested that cyclosporin A is primarily taken up from lipoprotein at the blood-brain interface but, because of tight junctions at the blood-brain and blood-CSF barriers, becomes effectively trapped in the cerebral endothelial cells and the choroid plexus.
Databáze: OpenAIRE
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