Effects of Maternal Antenatal Glucocorticoid Treatment on Apoptosis in the Ovine Fetal Cerebral Cortex

被引:20
作者
Malaeb, Shadi N.
Hovanesian, Virginia [2 ]
Sarasin, Matthew D.
Hartmann, Silvia M.
Sadowska, Grazyna B.
Stonestreet, Barbara S. [1 ]
机构
[1] Brown Univ, Warren Alpert Med Sch, Dept Pediat, Women & Infants Hosp Rhode Isl, Providence, RI 02912 USA
[2] Rhode Isl Hosp, Core Res Labs, Providence, RI USA
关键词
apoptosis; brain; caspase; development; fetus; maternal; sheep; steroids; PROGRAMMED CELL-DEATH; TISSUE WATER-CONTENT; WHITE-MATTER INJURY; OLIGODENDROCYTE PROGENITORS; BETAMETHASONE TREATMENT; CASPASE-3; ACTIVATION; NEURONAL APOPTOSIS; MULTIPLE COURSES; NEWBORN PIGLETS; NERVOUS-SYSTEM;
D O I
10.1002/jnr.21825
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We examined the effects of single and multiple maternal glucocorticoid courses on apoptosis in the cerebral cortices of ovine fetuses (CC). Ewes received single dexamethasone or placebo courses at 104-106 or 133135 days or multiple courses between 76-78 and 104106 days gestation. In the single-course groups, ewes received four 6 mg dexamethasone or placebo injections every 12 hr for 48 hr. Multiple-course groups received the same treatment once per week for 5 weeks. Neuronal and nonneuronal apoptotic cell numbers per square millimeter were determined with TUNEL and NeuN staining and with caspase-3 enzyme activity on CC tissues harvested at 106-108 (70%) or 135-137 (90%) days of gestation. Apoptotic cell numbers and caspase-3 activity were 50% lower (P < 0.02) after single placebo courses at 90% than 70% gestation; 90% of apoptotic cells were (P < 0.01) nonneuronal at both ages. Nonneuronal apoptotic cells and caspase-3 activity were 40% and 20% lower (P < 0.02) after single dexamethasone than placebo courses at 70%, but not 90%, gestation. Caspase-3 activity was 20% lower (P < 0.01) after multiple dexamethasone than placebo courses, but apoptotic cell number did not differ. We conclude that nonneuronal apoptosis represents the major form of apoptosis in the CC at both 70% and 90% of gestation. Apoptosis in nonneuronal cells decreases with maturity and after a single course of dexamethasone at 70%, but not at 90%, gestation and not after multiple courses at 70% gestation. We speculate that a single course of glucocorticoids exerts maturational changes on the rate of apoptosis in the cerebral cortex of preterm ovine fetuses. (C) 2008 Wiley-Liss, Inc.
引用
收藏
页码:179 / 189
页数:11
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