Biomedical subjects

G B Sadowska

Publications and source records attributed to G B Sadowska.

3 recordsLinked to original sources

PubMed2000

Effect of dexamethasone treatment on maturational changes in the NMDA receptor in sheep brain.

The objective of the present study was to examine the effect of antenatal or postnatal treatment with corticosteroids on the NMDA receptor, one of the mediators of both normal brain development and hypoxic-ischemic injury, by determining the characteristics of the receptor MK-801 binding site in untreated and corticosteroid-treated fetal and newborn lambs. (3)H-MK-801 binding was performed in cerebral cortical cell membranes from fetal sheep at 88, 120, and 136 d gestation (term = 150 d), and from 5-d-old lambs and adult ewes. Animals were randomized to receive dexamethasone [fetuses: 6 mg, i.m. every 12 hr for four doses to mother; lambs: 0.01 mg/kg (low dose) or 0.25 mg/kg (high dose) every 12 hr for four doses] or placebo. During development, B(max) (apparent number of receptors) increased, reaching a maximum in 5-d-old lambs (p < 0.05) and decreasing in the adult brain. K(d) (dissociation constant) did not change, suggesting that receptor affinity was not altered during maturation. Dexamethasone treatment had no effect on MK-801 binding in the fetus or adult, but in lambs was associated with a significant decrease in B(max) from 2.17 +/- 0.18 pmol/mg protein in placebo-treated animals to 1.65 +/- 0.8 and 1.62 +/- 0.07 pmol/mg protein in low-dose and high-dose animals, respectively. Affinity for (3)H-MK-801 decreased 20% after dexamethasone treatment in lambs only (p < 0.05). Thus, dexamethasone treatment appears to modify the NMDA receptor only during a specific period of brain development.

Animals↗

PubMed2000

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

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 (K(i)) to alpha-aminoisobutyric acid. K(i) 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 K(i) 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.

Adrenal Cortex Hormones↗

PubMed1999

Antenatal steroids decrease blood-brain barrier permeability in the ovine fetus.

Antenatal corticosteroid therapy reduces the incidence of intraventricular hemorrhage in premature infants. Enhanced microvascular integrity might provide protection against intraventricular hemorrhage. In the adult, there is evidence to suggest that the blood-brain barrier may be under hormonal control. We hypothesized that antenatal corticosteroids decrease blood-brain barrier permeability in the preterm ovine fetus. Chronically instrumented 120-day-gestation fetuses were studied 12 h after the last of four 6-mg dexamethasone (n = 5) or placebo (n = 6) injections had been given over 48 h to the ewes. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (Ki) for alpha-aminoisobutyric acid (AIB). Ki was significantly lower across brain regions in the fetuses of ewes that received antenatal dexamethasone compared with placebo (ANOVA; interaction, F = 2.54, P < 0.004). In fetuses of dexamethasone- and placebo-treated ewes, Ki (microliter . g brain wt-1. min-1, mean +/- SD) was, respectively, 2.43 +/- 0.27 vs. 3.41 +/- 0.74 in the cortex, 4.46 +/- 0.49 vs. 5.29 +/- 0.85 in the cerebellum, and 3.70 +/- 0.49 vs. 5.11 +/- 0.70 in the medulla. We conclude that antenatal treatment with corticosteroids reduces blood-brain permeability in the ovine fetus.

Adrenal Cortex Hormones↗