Effects of maternal treatment with corticosteroids on tight junction protein expression in the cerebral cortex of the ovine fetus with and without exposure to in utero brain ischemia.
Maternal treatment with corticosteroids reduces blood-brain barrier permeability in premature ovine fetuses and the incidence of intraventricular hemorrhage in premature infants. We tested the hypothesis that maternally administered corticosteroids increase the expression of tight junction (TJ) proteins in the cerebral cortex of ovine fetuses with and without exposure to in utero brain ischemia. Fetuses at 80% of gestation were studied 18 h after the last of four 4-6 mg dexamethasone or placebo injections were given over 48 h to ewes. Groups were placebo/control, dexamethasone/control, placebo/ischemic, and dexamethasone/ischemic. Ischemia consisted of 30 min of fetal carotid artery occlusion and 72 h of reperfusion. Cerebral cortex was snap frozen. Western immunoblot was used to measure the protein expression of occludin, claudin-1, claudin-5, zonula occludens (ZO)-1, and ZO-2, and a TJ accessory protein annexin-ll. Occludin and annexin-ll protein expression were 48% and 58% higher (P<0.05) in the dexamethasone/ischemic than placebo/control group, respectively. Claudin-5 protein expression was 69% and 73% higher (P<0.05) in the placebo/ischemic and dexamethasone/ischemic than placebo/control group. Claudin-1 expression did not differ among groups. ZO-1 protein expression was 25%, 40%, and 55% lower in the dexamethasone/control, placebo/ischemic, and dexamethasone/ischemic than placebo/control group, respectively. ZO-2 expression was 45% and 70% lower (P<0.01) in the placebo/ischemic and dexamethasone/ischemic than placebo/control group. We conclude that maternal corticosteroid treatment differentially regulates the expression of component proteins of TJs in the cerebral cortex of fetuses exposed to brain ischemia. The functional significance of this differential regulation warrants further investigation.
Malaeb
Shadi N
SN
Department of Pediatrics, Brown University School of Medicine, Women and Infants' Hospital of Rhode Island, 101 Dudley Street, Providence, RI 02905-240, USA.
Sadowska
Grazyna B
GB
Stonestreet
Barbara S
BS
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D008565:Membrane Proteins / Q000378:metabolism*; D011247:Pregnancy; D012756:Sheep / Q000196:embryology
D000305:Adrenal Cortex Hormones; D008565:Membrane Proteins; D003907:Dexamethasone