BRAIN-DAMAGE INDUCED BY PRENATAL EXPOSURE TO DEXAMETHASONE IN FETAL RHESUS MACAQUES .1. HIPPOCAMPUS
BRAIN-DAMAGE INDUCED BY PRENATAL EXPOSURE TO DEXAMETHASONE IN FETAL RHESUS MACAQUES .1. HIPPOCAMPUS
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DOI：
10.1016/0165-3806(90)90002-g
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发表时间：
1990-05-01
期刊：
影响因子：
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通讯作者：
FARRELL, PM
中科院分区：
文献类型：
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作者：
UNO, H;LOHMILLER, L;FARRELL, PM
在妊娠135和162天（足月为165天）的胎恒河猴脑中检查了产前给予地塞米松的神经毒性作用。在模拟人类临床试验的实验设计中，在第132天（以0.5、5或10 mg/kg母体体重的剂量单次注射）或在第132和133天（以12小时间隔多次注射0.125 × 10 mg/kg母体体重）将地塞米松肌内给予妊娠猴。4，1.25 ×4或2.5 mg/kg ×. 4）。在第135天和第162天通过剖腹产术分娩胎仔，并制备海马切片用于评价。光镜和电镜观察显示海马CA区锥体神经元和齿状回颗粒神经元数量减少，伴有神经元胞体和树突变性。海马CA 3区苔藓纤维轴树突触终末明显变性。变性是剂量依赖性的，多次注射比单次注射相同的总剂量诱导更严重的损伤。即使是最低剂量（0.5 mg/kg，与人体临床试验中使用的剂量相似）也会产生这些变化。第132天和第133天地塞米松给药（5 mg/kg）诱导的退行性变化在第162天研究的胎仔中也明显。因此，建议在早产时谨慎使用产前皮质类固醇。
Neurotoxic effects of prenatal administration of dexamethasone were examined in the fetal rhesus monkey brain at 135 and 162 days of gestation (term is 165 days). In an experimental design mimicking human clinical trials, dexamethasone was given intramuscularly to pregnant monkeys on day 132 (single injection with doses of 0.5, 5, or 10 mg/kg maternal body weight) or on days 132 and 133 (multiple injections at 12-h intervals with 0.125 .times. 4, 1.25 .times. 4, or 2.5 mg/kg .times. 4). The fetuses were delivered by caesarean section on day 135 days 162 and hippocampal slices were prepared for evaluation. Light and electron microscopic observation revealed decreased numbers of pyramidal neurons in the hippocampal CA regions and of granular neurons in the dentate gyrus associated with degeneration of neuronal perikarya and dendrites. Axodendritic synaptic terminals of the mossy fibers in the CA3 hippocampal region showed pronounced degeneration. Degeneration was dose-dependent and multiple injections induced more severe damage than single injections of the same total dose. Even the lowest dose (0.5 mg/kg, which is similar to the dose used in human clinical trials) produced these changes. Degenerative changes induced by dexamethasone treatment (5 mg/kg) on days 132 and 133 were also clearly evident in fetuses studied at 162 days. Therefore, caution is recommended in the use of prenatal corticosteroids in premature deliveries.