Disturbed flow disrupts the blood-brain barrier in a 3D bifurcation model
Disturbed flow disrupts the blood-brain barrier in a 3D bifurcation model
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DOI：
10.1088/1758-5090/ab5898
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发表时间：
2020-04-01
期刊：
影响因子：
9
通讯作者：
Galie, Peter A.
中科院分区：
文献类型：
--
作者：
Bouhrira, Nesrine;Deore, Brandon J.;Galie, Peter A.
在系统脉管系统中，干扰血流对内皮的影响已被广泛研究，但对血脑屏障（BBB）对这些血流机制的反应知之甚少。在这里，我们使用由内皮细胞、壁细胞和胶质细胞共培养组成的三维可灌注分叉模型来研究血流干扰对血脑屏障完整性的影响。通过计算流体动力学预测的实验流动模式模拟了体内的流动模式，特别是在分叉的下游存在一个再循环区。右旋糖酐渗透性测定和紧密连接标记的免疫染色表明，与分叉下游完全发达的区域相比，血流紊乱区域的屏障破坏明显更大。探测细胞类型之间的串扰表明，受干扰的血流会导致独立于内皮-壁和内皮-胶质相互作用的屏障破坏。总的来说，血流紊乱引起的血脑屏障破坏表明，血流介导的机制可能导致中枢神经系统的血管病变。
The effect of disturbed flow profiles on the endothelium have been studied extensively in systemic vasculature, but less is known about the response of the blood-brain barrier (BBB) to these flow regimes. Here we investigate the effect of disturbed flow on the integrity of the BBB using a three-dimensional, perfusable bifurcation model consisting of a co-culture of endothelial cells with mural and glial cells. Experimental flow patterns predicted by computational fluid dynamics mimic in vivo flow regimes, specifically the presence of a recirculation zone immediately downstream of the bifurcation. Dextran permeability assays and immunostaining with markers for tight junctions show that barrier disruption is significantly greater in areas of disturbed flow compared to fully developed regions downstream of the bifurcation. Probing crosstalk between cell types suggests that disturbed flow causes barrier breakdown independent of endothelial-mural and endothelial-glial interaction. Overall, disturbed flow-induced disruption of the blood-brain barrier suggests that flow-mediated mechanisms may contribute to vascular pathologies in the central nervous system.