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Effects of Multiple Courses of Antenatal Corticosteroids on Blood-Brain Barrier Permeability in the Ovine Fetus

Clifford S. Patlak, PhD

Katherine H. Petersson, PhD

Department of Pediatrics, Brown University Medical School, Women and Infants' Hospital of Rhode Island, Providence, RI; Department of Neurology, Cerebrovascular Research Center, University of Pennsylvania, Philadelphia, PA

Barbara S. Stonestreet, MD

Department of Pediatrics, Brown University Medical School, Women and Infants' Hospital of Rhode Island, Providence, RI; Department of Neurology, Cerebrovascular Research Center, University of Pennsylvania, Philadelphia, PA; BStonestreet{at}wihri.org

Objective: To test the hypothesis that multiple courses of antenatal corticosteroids accentuate the decreases in blood-brain barrier permeability observed after a single course of corticosteroids in pretern ovine fetuses.

Methods: Chronically instrumented 106-day gestation ovine fetuses were studied after single and multiple courses of dexamethasone or placebo were given to ewes beginning at 104 to 106 or 76 to 78 days of gestation, respectively. In the single-course groups, the ewes received dexamethasone (6 mg, n = 6) or placebo (n = 6) as four intramuscular injections every 12 hours over 48 hours. In the multiple course groups, the ewes received the same treatment (dexamethasone, n = 9, or placebo, n = 8), once per week for 5 weeks starting at 76 to 78 days of gestation. Blood-brain barrier permeability was quantified with the blood-to-brain transfer constant (K_i) for -aminoisobytyric acid (AIB) in the brain regions of the fetuses 12 hours after the last injection of dexamethasone was given to the ewes at 106 to 107 days of gestation.

Results: Both single (analysis of variance [ANOVA]; main effects for dexamethasone treatment, F = 5.92, P <.04) and multiple (ANOVA; main effects for dexamethasone treatment, F = 4.74, P <.04) course of antenatal corticosteriods were associated with decreases in blood-brain barrier permeability in the brain regions of the ovine fetus. However, the multiple course did not accentuate (ANOVA; main effects for single versus multiple courses, F = 1.06, P = .32) the decreases in permeability observed after a single course.

Conclusion: Contrary to our hypothesis, antenatal treatment with a 5-week course of corticosteroids did not accentuate the reductions in blood-brain barrier permeability that we observed after a single course of corticosteroids in the fetus.

Key Words: -aminoisobutyric acid • brain • development • dexamethasone • gestation • maturation • sheep • steroids

Journal of the Society for Gynecologic Investigation, Vol. 13, No. 4, 248-255 (2006)
DOI: 10.1016/j.jsgi.2006.02.012


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