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首页> 外文期刊>Biomaterials >In vitro evidence of dysregulation of blood-brain barrier function after acute and repeated/long-term exposure to TiO(2) nanoparticles.
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In vitro evidence of dysregulation of blood-brain barrier function after acute and repeated/long-term exposure to TiO(2) nanoparticles.

机译:急性和反复/长期暴露于TiO(2)纳米粒子后血脑屏障功能失调的体外证据。

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The effects of titanium dioxide nanoparticles (TiO(2) NPs) on blood-brain barrier (BBB) function are unknown. Here, we report such evidence of adverse effects after in vitro exposure of a rat primary cell-based BBB model to NPs. BBB integrity was studied by measuring the flux of sucrose through the monolayer. P-glycoprotein (P-gp) activity was assessed by measuring the passage of vinblastine. Transcription profiles of P-gp and other ABC transporters as well as of cytokines were investigated by real-time PCR. Electron microscopy and particle-induced X-ray emission measurements were performed. We compared several exposure modalities, from early to chronic, mimicking a brain-to-blood transport or a systemic contamination. In the first case, BBB integrity was preserved, but P-gp activity of endothelial cells (BECs) was reduced. In the second case, BBB integrity and P-gp function were impaired from 5 mug/mL for 24 h and expression of tight junction proteins and efflux transporters was modulated. An inflammatory response had repercussions on ABC transporter expression of glial cells. We demonstrate that NPs accumulated in BECs and crossed the cell monolayer. These findings suggest that there is an immunoregulatory loop between inflammatory components, BECs and glial cells in the dysfunction of the BBB during exposure to TiO(2) NPs.
机译:二氧化钛纳米粒子(TiO(2)NPs)对血脑屏障(BBB)功能的影响是未知的。在这里,我们报告了大鼠原代基于细胞的BBB模型体外暴露于NPs后的不利影响的证据。通过测量蔗糖通过单层的通量来研究BBB的完整性。通过测量长春碱的通过来评估P-糖蛋白(P-gp)的活性。通过实时PCR研究了P-gp和其他ABC转运蛋白以及细胞因子的转录谱。进行了电子显微镜和粒子诱导的X射线发射测量。我们比较了从早期到慢性的几种暴露方式,它们模拟了脑到血的运输或系统性污染。在第一种情况下,BBB的完整性得以保留,但内皮细胞(BEC)的P-gp活性却降低了。在第二种情况下,从5杯/毫升的BBB完整性和P-gp功能受损24小时,并调节紧密连接蛋白和外排转运蛋白的表达。炎性反应对神经胶质细胞的ABC转运蛋白表达有影响。我们证明NPs在BEC中积累并越过细胞单层。这些发现表明,在暴露于TiO(2)NP的过程中,BBB功能障碍的炎症成分,BEC和神经胶质细胞之间存在免疫调节环。

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