Repeated prenatal corticosteroid administration delays astrocyte and capillary tight junction maturation in fetal sheep

Glucocorticoids are powerful regulators of cell differentiation and maturat ion. Their synthetic counterparts, the corticosteroids, are used widely in obstetric practice to enhance fetal lung maturation in cases of threatened preterm birth. Here we examined the effects of repeated corticosteroid admi nistration on astrocyte and capillary tight junction development in the fet al sheep brain, selecting the corpus callosum for analysis. Pregnant ewes w ere given saline or betamethasone (0.5 mg/kg) at 104, 111, 118 and 124 days gestation, Lambs were delivered at term, terminally anaesthetized and tran scardially perfused. Transverse semi-thin sections of the corpus callosum w ere cut and immuno-stained with antibody against glial fibrillary acidic pr otein (GFAP). Ultra-thin sections were examined in the electron microscope. The percentage area of GFAP staining was reduced in the corticosteroid-tre ated group compared to control (5.2 vs. 8.7%, P < 0.05). The expression of GFAP in peri-capillary and parenchymal astrocytes was also reduced compared to control (peri-capillary: 3.0 vs. 9.5 mum(2); parenchymal: 14.6 vs. 29.4 mum(2), P < 0.05). Furthermore, capillary tight junction maturation was de layed compared to control. Immature 'type II' junctions were more common in the corticosteroid-treated group (63 vs. 22%, P < 0.05), whereas more matu re 'type III' junctions were less common (27 vs. 65%, P < 0.05). Our data s uggest that repeated corticosteroids delay both astrocyte and capillary tig ht junction maturation. The implications for clinical practice are as yet u nknown. (C) 2001 ISDN. Published by Elsevier Science Ltd. All rights reserv ed.