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Am J Physiol Regul Integr Comp Physiol 279: R468-R477, 2000;
0363-6119/00 $5.00
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Vol. 279, Issue 2, R468-R477, August 2000

Exogenous and endogenous corticosteroids modulate blood-brain barrier development in the ovine fetus

Barbara S. Stonestreet1, Grazyna B. Sadowska1, Amanda J. McKnight1, Clifford Patlak2, and Katherine H. Petersson1

1 Department of Pediatrics, Women and Infants Hospital of Rhode Island, Brown University School of Medicine, Providence, Rhode Island 02905; and 2 Department of Surgery, State University of New York at Stony Brook, Stony Brook, New York 11794-8191

We previously reported decreases in blood-brain barrier permeability in the ovine fetus at 80% of gestation after antenatal corticosteroids and shown that permeability is not reduced in newborn lambs after postnatal corticosteroids. We now test the hypotheses that exogenous antenatal corticosteroids decrease blood-brain barrier permeability at 60% but not 90% of gestation in ovine fetuses and that endogenous increases in plasma cortisol concentrations are associated with ontogenic decreases in barrier permeability during gestation. Chronically instrumented ovine fetuses were studied 12 h after the last of four 6-mg dexamethasone or placebo injections were given 12 h apart over 48 h to ewes. Fetuses at 80% of gestation from placebo-treated ewes studied under the same protocol were also included. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (Ki) to alpha -aminoisobutyric acid. Ki values were lower in cerebral cortex, caudate nucleus, hippocampus, superior colliculus, thalamus, medulla, and cervical spinal cord in fetuses of dexamethasone- than placebo-treated ewes at 60% but not 90% of gestation. Regional brain Ki values demonstrated inverse correlations with increases in gestation and plasma cortisol concentrations in most brain regions. We conclude that maternal treatment with exogenous corticosteroids was associated with decreases in blood-brain barrier permeability at 60% but not 90% of gestation and that increases in gestation and endogenous cortisol concentrations were associated with ontogenic decreases in barrier permeability during fetal development.

alpha-aminoisobutyric acid; brain; cortisol; gestation; maturation; sheep; steroids


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