Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice.
Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice.
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DOI：
10.1186/1743-8977-10-62
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发表时间：
2013-12-17
影响因子：
10
通讯作者：
Lund AK
中科院分区：
文献类型：
--
作者：
Oppenheim HA;Lucero J;Guyot AC;Herbert LM;McDonald JD;Mabondzo A;Lund AK
在人类暴露和动物模型中，暴露于有毒气体产生的空气污染与中枢神经系统（CNS）的不良影响有关，包括神经炎症和神经变性。虽然血脑屏障（BBB）的改变已被认为是空气污染诱导的CNS病理学的潜在机制，但涉及的途径尚未阐明。确定吸入暴露于混合车辆废气（MVE）是否介导BBB通透性的改变、基质金属蛋白酶（MMP）-2和-9的活化以及紧密连接（TJ）蛋白表达的改变。将载脂蛋白（Apo）E−/−和C57 B16小鼠暴露于MVE（100 μg/m3 PM）或过滤空气（FA）中，每天6小时，持续30天，并评估所产生的BBB通透性、ROS表达、TJ蛋白、神经炎症标志物和MMP活性。将来自研究小鼠的血清应用于体外BBB共培养模型，并定量运输和渗透性的变化。与FA对照组相比，MVE暴露的Apo E−/−小鼠显示BBB通透性增加，ROS升高，MMP-2和-9活性增加。此外，暴露于MVE的小鼠的脑血管表达了TJ蛋白、闭合蛋白和封闭蛋白-5水平的降低，以及实质中诱导型一氧化氮合酶（iNOS）和白细胞介素（IL）-1β水平的增加。来自MVE暴露动物的血清也导致体外BBB通透性增加和P-糖蛋白转运活性改变。这些数据表明，吸入暴露于交通产生的空气污染物促进MMP活性增加和TJ蛋白在脑血管系统中的降解，导致改变BBB通透性和神经炎症标志物的表达。
Traffic-generated air pollution-exposure is associated with adverse effects in the central nervous system (CNS) in both human exposures and animal models, including neuroinflammation and neurodegeneration. While alterations in the blood brain barrier (BBB) have been implicated as a potential mechanism of air pollution-induced CNS pathologies, pathways involved have not been elucidated. To determine whether inhalation exposure to mixed vehicle exhaust (MVE) mediates alterations in BBB permeability, activation of matrix metalloproteinases (MMP) -2 and −9, and altered tight junction (TJ) protein expression. Apolipoprotein (Apo) E−/− and C57Bl6 mice were exposed to either MVE (100 μg/m3 PM) or filtered air (FA) for 6 hr/day for 30 days and resulting BBB permeability, expression of ROS, TJ proteins, markers of neuroinflammation, and MMP activity were assessed. Serum from study mice was applied to an in vitro BBB co-culture model and resulting alterations in transport and permeability were quantified. MVE-exposed Apo E−/− mice showed increased BBB permeability, elevated ROS and increased MMP-2 and −9 activity, compared to FA controls. Additionally, cerebral vessels from MVE-exposed mice expressed decreased levels of TJ proteins, occludin and claudin-5, and increased levels of inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β in the parenchyma. Serum from MVE-exposed animals also resulted in increased in vitro BBB permeability and altered P-glycoprotein transport activity. These data indicate that inhalation exposure to traffic-generated air pollutants promotes increased MMP activity and degradation of TJ proteins in the cerebral vasculature, resulting in altered BBB permeability and expression of neuroinflammatory markers.
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影响因子：
5.8
作者：
Beauloye, Veronique;Zech, Francis;Brichard, Sonia M.
通讯作者：
Brichard, Sonia M.
影响因子：
8.3
作者：
Elali, Ayman;Doeppner, Thorsten R.;Hermann, Dirk M.
通讯作者：
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影响因子：
15.9
作者：
Block, Michelle L.;Calderon-Garciduenas, Lilian
通讯作者：
Calderon-Garciduenas, Lilian
影响因子：
3.7
作者：
Farina F;Sancini G;Battaglia C;Tinaglia V;Mantecca P;Camatini M;Palestini P
通讯作者：
Palestini P
影响因子：
3.1
作者：
Fricker, G;Miller, DS
通讯作者：
Miller, DS