Regional alterations in blood-to-brain transfer of alpha-aminoisobutyric acid and sucrose, after chronic administration and withdrawal of dexamethasone.
The effect of dexamethasone administration and withdrawal was studied with respect to blood-brain barrier function. The tracers alpha-[3H]aminoisobutyric acid (AIB) (MW 104) and [14C]sucrose (MW 342), which have a low permeability across the intact endothelium, were simultaneously injected intravenously in rats treated with dexamethasone and placebo-treated control animals or in rats in which dexamethasone treatment was discontinued 3 days before the experiment. Unidirectional transfer constants (Ki) were determined in discrete brain regions. Steroid administration reduced the rate of influx of AIB and sucrose, whereas discontinuation of drug resulted in an increased permeability. These findings suggest that when exposure to glucocorticoids is prolonged, the efficiency of medical treatment of CNS diseases may decrease due to reduction of drug delivery to CNS. Thus, these experimental findings may have particular importance in the clinical setting of drug administration when considering the combination of steroids with other drugs, and may aid in understanding better the pathogenesis of some types of brain edema seen in patients from whom corticosteroid therapy has been withdrawn.
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*; D002199:Capillary Permeability / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000378:metabolism*
D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; D013395:Sucrose; D003907:Dexamethasone