Air Pollution Particulate Matter Exposure and Chronic Cerebral Hypoperfusion and Measures of White Matter Injury in a Murine Model,Environmental Health Perspectives

当前位置： X-MOL 学术 › Environ. Health Perspect. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Air Pollution Particulate Matter Exposure and Chronic Cerebral Hypoperfusion and Measures of White Matter Injury in a Murine Model
Environmental Health Perspectives ( IF 10.1 ) Pub Date : 2021-8-23 , DOI: 10.1289/ehp8792
Qinghai Liu ₁ , Kristina Shkirkova ₁ , Krista Lamorie-Foote ₁ , Michelle Connor ₂ , Arati Patel ₃ , Robin Babadjouni ₄ , Mikko Huuskonen _{1,

5} , Axel Montagne _{1,

5} , Hans Baertsch ₁ , Hongqiao Zhang ₆ , Jiu-Chiuan Chen ₇ , Wendy J Mack ₇ , Brian P Walcott ₈ , Berislav V Zlokovic _{1,

5} , Constantinos Sioutas ₉ , Todd E Morgan ₆ , Caleb E Finch ₆ , William J Mack _{1,

10}

Affiliation

Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California, USA.
Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Neurological Surgery, University of California San Francisco School of Medicine, San Francisco, California, USA.
Department of Neurological Surgery, Cedars-Sinai, Los Angeles, California, USA.
Department of Physiology and Neuroscience, University of Southern California, Los Angeles, California, USA.
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Department of Preventative Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California, USA.
Department of Neurosurgery, Northshore Neurological Institute, Evanston, Illinois, USA.
Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, USA.
Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Abstract

Background:

Exposure to ambient air pollution particulate matter (PM) is associated with increased risk of dementia and accelerated cognitive loss. Vascular contributions to cognitive impairment are well recognized. Chronic cerebral hypoperfusion (CCH) promotes neuroinflammation and blood–brain barrier weakening, which may augment neurotoxic effects of PM.

Objectives:

This study examined interactions of nanoscale particulate matter (nPM; fine particulate matter with aerodynamic diameter $less than or equal to 200 nanometers$ ) and CCH secondary to bilateral carotid artery stenosis (BCAS) in a murine model to produce white matter injury. Based on other air pollution interactions, we predicted synergies of nPM with BCAS.

Methods:

nPM was collected using a particle sampler near a Los Angeles, California, freeway. Mice were exposed to 10 wk of reaerosolized nPM or filtered air (FA) for 150 h. CCH was induced by BCAS surgery. Mice (C57BL/6J males) were randomized to four exposure paradigms: a) FA, b) nPM, c) $FA + BCAS$ , and d) $nPM + BCAS$ . Behavioral outcomes, white matter injury, glial cell activation, inflammation, and oxidative stress were assessed.

Results:

The joint $nPM + BCAS$ group exhibited synergistic effects on white matter injury (2.3× the additive nPM and $FA + BCAS$ scores) with greater loss of corpus callosum volume on T2 magnetic resonance imaging (MRI) (30% smaller than FA group). Histochemical analyses suggested potential microglial-specific inflammatory responses with synergistic effects on corpus callosum C5 immunofluorescent density and whole brain nitrate concentrations (2.1× and 3.9× the additive nPM and $FA + BCAS$ effects, respectively) in the joint exposure group. Transcriptomic responses (RNA-Seq) showed greater impact of $nPM + BCAS$ than individual additive effects, consistent with changes in proinflammatory pathways. Although nPM exposure alone did not alter working memory, the $nPM + BCAS$ cohort demonstrated impaired working memory when compared to the $FA + BCAS$ group.

Discussion:

Our data suggest that nPM and CCH contribute to white matter injury in a synergistic manner in a mouse model. Adverse neurological effects may be aggravated in a susceptible population exposed to air pollution. https://doi.org/10.1289/EHP8792

中文翻译：

小鼠模型中空气污染颗粒物暴露与慢性脑灌注不足以及白质损伤的测量

抽象的

背景：

暴露于环境空气污染颗粒物 (PM) 会增加患痴呆症的风险并加速认知能力丧失。血管对认知障碍的影响已得到广泛认可。慢性脑灌注不足 (CCH) 会促进神经炎症和血脑屏障减弱，这可能会增强 PM 的神经毒性作用。

目标：

这项研究考察了纳米级颗粒物（nPM；细颗粒物与空气动力学直径 $less than or equal to 200 nanometers$ ）和继发于小鼠模型中双侧颈动脉狭窄（BCAS）的 CCH 产生白质损伤。根据其他空气污染相互作用，我们预测了 nPM 与 BCAS 的协同作用。

方法：

nPM 是使用加利福尼亚州洛杉矶高速公路附近的颗粒采样器收集的。将小鼠暴露于重新雾化的 nPM 或过滤空气 (FA) 中 10 周 150 小时。 CCH 是由 BCAS 手术诱发的。小鼠（C57BL/6J 雄性）被随机分配到四种暴露模式： a ) FA、 b ) nPM、 c ) $FA + BCAS$ 和d ) $正PM + BCAS$ 。评估了行为结果、白质损伤、神经胶质细胞活化、炎症和氧化应激。

结果：

联合 $正PM + BCAS$ 组对白质损伤表现出协同作用（2.3×加性nPM和 $FA + BCAS$ T2 磁共振成像 (MRI) 上胼胝体体积损失更大（比 FA 组小 30%）。组织化学分析表明潜在的小胶质细胞特异性炎症反应对胼胝体 C5 免疫荧光密度和全脑硝酸盐浓度具有协同作用（nPM 和 NPM 附加值的 2.1 倍和 3.9 倍） $FA + BCAS$ 分别影响）在联合暴露组中。转录组反应（RNA-Seq）显示出更大的影响 $正PM + BCAS$ 比个体累加效应，与促炎症途径的变化一致。虽然单独接触 nPM 并不会改变工作记忆，但 $正PM + BCAS$ 与对照组相比，队列表现出工作记忆受损 $FA + BCAS$ 团体。

讨论：

更新日期：2021-08-23

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11