Effect of dexamethasone on transport of alpha-aminoisobutyric acid and sucrose across the blood-brain barrier.
The effect of glucocorticoids on the blood-brain barrier (BBB) was studied in rats following a single injection or 3 days of dexamethasone administration. Tracers with a low permeability across the intact endothelium, [14C]sucrose and alpha-[3H]aminoisobutyric acid ([3H]AIB), were simultaneously injected intravenously in untreated rats or in rats treated with dexamethasone. Unidirectional blood-to-brain transfer constants (Ki) in 14 regions of the rat brain were determined. In regions of control brain, average Ki values for AIB and sucrose were approximately 0.0020 and 0.00060 ml g-1 min-1, respectively. The lowest transfer constants were found in caudate nucleus, hippocampus, white matter, and cerebellum. In dexamethasone-treated animals, Ki values for both sucrose and AIB markedly decreased by 30-50% in almost all brain regions. These results indicate that a single injection or 3 days of treatment with dexamethasone causes an apparent reduction in the normal BBB permeability, and dexamethasone may greatly interfere with drug delivery into brain. These observations may have an importance for the administration of drugs in brain disease in the presence of steroids.
Ziylan
Y Z
YZ
Unité de Neurotoxicologie, INSERM U. 26, Hôpital Fernand Widal, Paris, France.
LeFauconnier
J M
JM
Bernard
G
G
Bourre
J M
JM
D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism
D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; D013395:Sucrose; D003907:Dexamethasone