Dataset Information

Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet.

ABSTRACT: Air pollution-exposure is associated with detrimental outcomes in the central nervous system (CNS) such as cerebrovascular disorders, including stroke, and neurodegenerative diseases. While the mechanisms of these CNS-related outcomes involved have not been fully elucidated, exposure to traffic-generated air pollutants has been associated with altered blood brain barrier (BBB) integrity and permeability. The current study investigated whether inhalation exposure to mixed vehicle emissions (MVE) alters cerebral microvascular integrity in healthy 3 mo old C57BL/6 mice, as well as whether exposure-mediated effects were exacerbated by a high-fat (HF) vs. low-fat (LF) diet. Mice on each diet were randomly assigned to be exposed to either filtered air (FA) or MVE [100PM/m3 vehicle emissions mixture: 30µg PM/m3 gasoline engine + 70µg PM/m3 diesel engine emissions; median size ~ 60nm; particle mass size distribution median of ~ 1µm (range: < 0.5-20µm)] for 6h/d, 7d/wk, for 30d. Using sodium fluorescein as a tracer, we observed a significant increase in BBB permeability in both HF + MVE exposed and HF + FA animals, compared to LF + FA controls. Exposure to HF + MVE also led to a significant increase plasma ox-LDL and ox-LDL scavenger receptors (LOX-1 and CD-36) expression in the cerebral vasculature. Histological analysis revealed decreased expression of TJ protein, claudin-5, associated with increased matrix metalloproteinase (MMP)-9 activity and oxidative stress in the cerebral vasculature of HF + MVE mice, compared to LF + MVE. Such findings indicate that inhalation exposure to traffic-generated pollutants, coupled with a HF diet, results in altered BBB integrity and increased ox-LDL signaling in the cerebral vasculature in a wildtype animal model.

SUBMITTER: Suwannasual U

PROVIDER: S-EPMC5705467 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet.

Suwannasual Usa U Lucero JoAnn J McDonald Jacob D JD Lund Amie K AK

Environmental research 20171105

Air pollution-exposure is associated with detrimental outcomes in the central nervous system (CNS) such as cerebrovascular disorders, including stroke, and neurodegenerative diseases. While the mechanisms of these CNS-related outcomes involved have not been fully elucidated, exposure to traffic-generated air pollutants has been associated with altered blood brain barrier (BBB) integrity and permeability. The current study investigated whether inhalation exposure to mixed vehicle emissions (MVE) ...[more]

PMID: 29073573

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Project description:Background:Air pollution exposures are novel contributors to the growing childhood obesity epidemic. One possible mechanism linking air pollution exposures and obesity is through changes in food consumption patterns. Objective:The aim of this study was to examine the longitudinal association between childhood exposure to air pollutants and changes in diet among adolescents. Design:School-age children were enrolled in the Southern California Children's Health Study during 1993-1994 (n = 3100) and were followed for 4-8 y. Community-level regional air pollutants [e.g., nitrogen dioxide (NO2), elemental carbon (EC), and fine particles with aerodynamic diameter <2.5 µm (PM2.5)] were measured at central monitoring stations. Line dispersion modeling was used to estimate concentrations of traffic-related air pollutants based on nitrogen oxides (NOx) at participants' residential addresses. In addition, self-reported diet information was collected annually using a structured youth/adolescent food-frequency questionnaire during 1997-2001. Generalized linear mixed-effects models were used in the association analyses. Results:Higher exposures to regional and traffic-related air pollutants were associated with intake of a high-trans-fat diet, after adjusting for confounders including socioeconomic status and access to fast food in the community. A 2-SD (12.2 parts per billion) increase in regional NO2 exposure was associated with a 34% increased risk of consuming a high-trans-fat diet compared with a low-trans-fat diet (OR: 1.34; 95% CI: 1.05, 1.72). In addition, higher exposures to acid vapor, EC, PM2.5, and non-freeway NOx were all associated with higher consumption of dietary trans fat (all P < 0.04). Notably, higher exposures to regional NO2, acid vapor, and EC were also associated with a higher consumption of fast food (all P < 0.05). Conclusions:Childhood exposures to regional and traffic-related air pollutants were associated with increased consumption by adolescents of trans fat and fast foods. Our results indicate that air pollution exposures may contribute to obesogenic behaviors. This study was registered at clinicaltrials.gov as NCT03379298.

Project description:Vehicles are major sources of air pollutant emissions, and individuals living near large roads endure high exposures and health risks associated with traffic-related air pollutants. Air pollution epidemiology, health risk, environmental justice, and transportation planning studies would all benefit from an improved understanding of the key information and metrics needed to assess exposures, as well as the strengths and limitations of alternate exposure metrics. This study develops and evaluates several metrics for characterizing exposure to traffic-related air pollutants for the 218 residential locations of participants in the NEXUS epidemiology study conducted in Detroit (MI, USA). Exposure metrics included proximity to major roads, traffic volume, vehicle mix, traffic density, vehicle exhaust emissions density, and pollutant concentrations predicted by dispersion models. Results presented for each metric include comparisons of exposure distributions, spatial variability, intraclass correlation, concordance and discordance rates, and overall strengths and limitations. While showing some agreement, the simple categorical and proximity classifications (e.g., high diesel/low diesel traffic roads and distance from major roads) do not reflect the range and overlap of exposures seen in the other metrics. Information provided by the traffic density metric, defined as the number of kilometers traveled (VKT) per day within a 300 m buffer around each home, was reasonably consistent with the more sophisticated metrics. Dispersion modeling provided spatially- and temporally-resolved concentrations, along with apportionments that separated concentrations due to traffic emissions and other sources. While several of the exposure metrics showed broad agreement, including traffic density, emissions density and modeled concentrations, these alternatives still produced exposure classifications that differed for a substantial fraction of study participants, e.g., from 20% to 50% of homes, depending on the metric, would be incorrectly classified into "low", "medium" or "high" traffic exposure classes. These and other results suggest the potential for exposure misclassification and the need for refined and validated exposure metrics. While data and computational demands for dispersion modeling of traffic emissions are non-trivial concerns, once established, dispersion modeling systems can provide exposure information for both on- and near-road environments that would benefit future traffic-related assessments.

Dataset Information

Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet.

Publications

Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet.

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