ANTENATAL STEROIDS DECREASE BLOOD-BRAIN BARRIER PERMEABILITY IN THE OVINE FETUS • 1067

Abstract

Antenatal corticosteroid therapy reduces the incidence of intraventricular hemorrhage (IVH). The mechanism(s) for this effect are not well understood. We have been interested in the development of the blood-brain barrier (BBB) as an important maturational event, which may confer microvascular integrity and protection against IVH. Maturation of the BBB may be under hormonal control. We hypothesized that antenatal corticosteroids decrease BBB permeability in the ovine fetus. Chronically instrumented 120 days of gestation (term=150 days) ovine fetuses were studied 12 hrs after the last of four 6 mg dexamethasone (n=5) or placebo (n=6) injections had been given over 48 hrs to the ewes. BBB function was quantified with the blood-to-brain transfer constant (Ki) to α-aminoisobutyric acid. Ki was significantly (ANOVA, P<0.004) lower across brain regions in fetuses of ewes which received antenatal dexamethasone compared with placebo (cerebrum: 2.45±0.27 vs 3.41±0.74; cerebellum: 4.55±0.48 vs 5.40±0.85; caudate nucleus: 1.89±0.12 vs 2.58±0.50; hippocampus: 2.17±0.19 vs 2.95±0.40; thalmus: 2.51±0.31 vs 3.46±0.55; medulla: 3.86±0.50 vs 5.25±0.71; and cervical spinal cord: 3.47±0.45 vs 4.89±0.66 m±SD, mL•g Brain-1•min-1). We conclude that antenatal treatment with corticosteroids reduces BBB permeability in the ovine fetus at 80% of gestation. We speculate that antenatal steroids accelerate maturation of the fetal BBB. Decreased barrier permeability reflecting endothelial vascular change arising from increased tight junction bonding may be one of the mechanisms by which antenatal corticosteroids reduce the incidence of IVH in very low birth weight infants. Supported by NIH HD/NS 34618-01