A novel brain neurovascular unit model with neurons, astrocytes and microvascular endothelial cells of rat.

A novel brain neurovascular unit model with neurons, astrocytes and microvascular endothelial cells of rat.
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一种新型大鼠神经元、星形胶质细胞和微血管内皮细胞脑神经血管单元模型

DOI:
10.7150/ijbs.5115
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发表时间:
2013
影响因子:
9.2
通讯作者:
Xu X
Xu X
中科院分区:
生物学2区
文献类型:
--
作者:
Xue Q;Liu Y;Qi H;Ma Q;Xu L;Chen W;Chen G;Xu X

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本研究建立了神经元、脑微血管内皮细胞(BMECs)和星形胶质细胞共培养的新型三细胞神经血管单元(NVU)模型,用于脑疾病的研究和治疗药物的筛选。我们首先对共培养模型进行了细胞鉴定和形态学表征,分析了特异性蛋白表达,并测定了正常情况下的血脑屏障(BBB)功能。然后,我们进一步测定缺氧-复氧后该模型血脑屏障功能、炎症、细胞损伤及神经保护因子的变化。结果表明,与bmec单独培养或与星形胶质细胞或神经元共培养相比,该模型具有更好的血脑屏障功能,p -糖蛋白(Pg-P)和ZO-1的表达显著增加。缺氧-复氧后,该模型的病理变化与体内脑细胞及血脑屏障的病理变化基本相似。尼莫地平,一种钙的拮抗剂,也可以逆转这些变化。根据我们的观察,我们推断这种三细胞共培养模型展示了NVU的基本结构、功能和细胞间相互作用,这可能为进一步研究脑疾病和药物筛选提供更合适的NVU体外体系。
A novel triple cell neurovascular unit (NVU) model co-culturing with neurons, brain microvascular endothelial cells (BMECs) and astrocytes was established in this study for investigating the cerebral diseases and screening the candidates of therapeutic drug. We have first performed the cell identification and morphological characterization, analyzed the specific protein expression and determined the blood-brain barrier (BBB) function of the co-culture model under normal condition. Then, we further determined the BBB function, inflammation, cell injury and the variation of neuroprotective factor in this model after anoxia-reoxygenation. The results suggest that this model exhibited a better BBB function and significantly increased expression of P-glycoprotein (Pg-P) and ZO-1 compared with BMECs only or co-culture with astrocytes or neurons. After anoxia-reoxygenation, the pathological changes of this model were basically resemblance to the pathological changes of brain cells and BBB in vivo. And nimodipine, an antagonist of calcium, could reverse those changes as well. According to our observations, we deduce that this triple cell co-culture model exhibits the basic structure, function and cell-cell interaction of NVU, which may offer a more proper in vitro system of NVU for the further investigation of cerebral diseases and drug screening.
DOI: 10.1083/jcb.85.3.890
发表时间: 1980-06
期刊: The Journal of cell biology
影响因子: --
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DOI: 10.1097/00001756-200112210-00055
发表时间: 2001-12-21
期刊: NEUROREPORT
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发表时间: 1993-06-04
期刊: BRAIN RESEARCH
影响因子: 2.9
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发表时间: 1995-08-01
影响因子: 5
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