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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Newborn- and adult-derived brain microvascular endothelial cells show age-related differences in phenotype and glutamate-evoked protease release.
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Newborn- and adult-derived brain microvascular endothelial cells show age-related differences in phenotype and glutamate-evoked protease release.

机译:新生儿和成人来源的脑微血管内皮细胞在表型和谷氨酸诱发的蛋白酶释放方面表现出与年龄相关的差异。

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摘要

Few data are available on the involvement of brain microvascular endothelial cells (BMECs) in excitotoxic neonatal brain lesions. Therefore, we developed an original approach for investigating mouse-derived BMECs in vitro. We hypothesized that newborn and adult BMEC cultures would show age-related differences in phenotype and sensitivity to glutamate. Expression of the monocarboxylate transporter, MCT1, was higher in neonatal than in adult BMECs, whereas expression of the glucose transporter, GLUT1, was higher in adult than in neonatal BMECs that overexpressed the N-methyl-D-aspartate receptor NR1 subunit (NMDAR1) compared with adult BMECs. The ability of neonatal and adult BMECs to be activated by glutamate was confirmed through intracellular calcium ([Ca2+]i) recording. The glutamate-induced [Ca2+]i increase was blocked by the selective NMDAR antagonist, MK-801. Significant glutamate-evoked concentration-dependent release of tissue-type plasminogen activator (t-PA) and matrix metalloproteinases (MMPs) activities was found in supernatants of neonatal, but not in adult BMECs. The glutamate-mediated release of t-PA, MMP-2, and MMP-9 proteolytic activities in neonatal BMECs was blocked by MK-801. Conceivably, this protease release from neonatal BMECs may participate in neonatal brain lesions.
机译:关于兴奋性毒性新生儿脑病变中涉及的脑微血管内皮细胞(BMEC)的资料很少。因此,我们开发了一种新颖的方法,用于体外研究小鼠衍生的BMEC。我们假设,新生和成年BMEC文化将在表型和对谷氨酸的敏感性方面显示出与年龄相关的差异。新生儿中单羧酸盐转运蛋白MCT1的表达高于成人BMEC,而成人中葡萄糖转运蛋白GLUT1的表达高于过表达N-甲基-D-天冬氨酸受体NR1亚基(NMDAR1)的新生儿BMEC。与成人BMEC相比。通过细胞内钙([Ca2 +] i)记录证实了新生和成年BMEC被谷氨酸激活的能力。选择性NMDAR拮抗剂MK-801阻止了谷氨酸诱导的[Ca2 +] i的增加。在新生儿的上清液中发现了谷氨酸引起的浓度依赖性的组织型纤溶酶原激活物(t-PA)和基质金属蛋白酶(MMPs)释放,而在成年BMEC中则没有。谷氨酸介导的新生BMECs中t-PA,MMP-2和MMP-9蛋白水解活性的释放被MK-801阻断。可以想象,这种从新生儿BMEC中释放的蛋白酶可能参与了新生儿脑部病变。

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