Altered functional development of the blood-brain barrier after early life stress in the rat
Altered functional development of the blood-brain barrier after early life stress in the rat
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DOI：
10.1016/j.brainresbull.2009.05.012
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发表时间：
2009-08-14
影响因子：
3.8
通讯作者：
Escobara, A.
中科院分区：
文献类型：
--
作者：
Gomez-Gonzalez, B.;Escobara, A.
本研究探讨了早期生活压力对哺乳动物Wistar大鼠血脑屏障功能发育的影响。怀孕大鼠在妊娠10-20天之间强迫游泳作为应激过程。分娩后，一半的对照窝在出生后2-20天与母亲分离180分钟。对照组没有任何压力操纵。在出生后1-30天的牺牲期间，受试者被给予心脏内埃文斯蓝或凝集素小麦胚芽凝集素结合辣根过氧化物酶（WGA-HRP）。对Evans蓝染色的脑切片进行拍照并测定光密度。对WGA-HRP染色的脑组织进行超微结构分析。用放射免疫法测定胚胎第20天和出生后第1、10、20、30天血浆皮质酮含量。出生后第10天，应激使Evans蓝进入新皮质、海马、间脑、基底节区、嗅球、脑干、小脑增加。还有脊髓。在产后第20天，产前压力增加了埃文斯蓝浓度的区域与产后压力后受影响的区域相同。在出生后10-20天，两个应激组海马毛细血管中WGA-HRP小泡介导的转运增加。在出生后第30天，对照组和应激鼠的血脑屏障功能成熟。与对照组相比，妊娠应激母鼠血浆皮质酮浓度较高。产后应激使产后第10天和第20天血浆皮质酮升高。研究结果表明，慢性围产期应激通过增加脑内皮细胞的小泡介导的运输来改变血脑屏障功能的发育。(C) 2009爱思唯尔公司版权所有。
This study investigated the effect of early life stress on blood-brain barrier functional development in an altricial mammal, the Wistar rat. Forced swimming between gestational days 10-20 was used as a stress procedure in pregnant rats. After delivery, half of the control litters underwent 180 min maternal separation from postnatal day 2-20. Controls were kept without any stress manipulations. At sacrifice between postnatal days 1-30 subjects were given intracardiac Evans blue or the lectin wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Evans blue-stained brain slices were photographed and optical density quantified. WGA-HRP stained brains were processed for ultrastructural analysis. Plasma corticosterone at embryonic day 20 and postnatal days 1, 10, 20 and 30 was quantified by radioimmunoassay. At postnatal day 10, postnatal stress increased Evans blue entry to the neocortex, hippocampus, diencephalon, basal ganglia, olfactory bulb, brain stem, cerebellum. and spinal cord. At postnatal day 20, prenatal stress increased Evans blue concentration in the same regions as those affected after postnatal stress. Between postnatal days 10-20, both stress groups showed increased WGA-HRP caveolae-mediated transport in the hippocampal capillaries. By postnatal day 30, the blood-brain barrier was functionally mature in both control and stressed pups. Plasma corticosterone concentration was higher in pregnant stressed dams as compared to controls. Postnatal stress increased plasma corticosterone at postnatal days 10 and 20. The findings suggest that chronic perinatal stress alters blood-brain barrier functional development by increasing caveolae-mediated transport in brain endothelial cells. (C) 2009 Elsevier Inc. All rights reserved.