Air Pollution Particulate Matter Exposure and Chronic Cerebral Hypoperfusion and Measures of White Matter Injury in a Murine Model.

Autor: Qinghai Liu1, Shkirkova, Kristina1, Lamorie-Foote, Krista1, Connor, Michelle2, Patel, Arati3, Babadjouni, Robin4, Huuskonen, Mikko1,5, Montagne, Axel1,5, Baertsch, Hans1, Hongqiao Zhang6, Jiu-Chiuan Chen7, Mack, Wendy J.7, Walcott, Brian P.8, Zlokovic, Berislav V.1,5, Sioutas, Constantinos9, Morgan, Todd E.6, Finch, Caleb E.6, Mack, William J.1,10 William.Mack@med.usc.edu
Předmět:
*Air pollution
*Particulate matter
*Animal behavior
*Aerosols
*Air filters
*Animal experimentation
*Nitrates
*RNA
*Environmental exposure
Dementia risk factors
Cognition disorder risk factors
Nitrate analysis
Protein analysis
Neurotoxicology
Aerodynamics
Biological models
Body composition
Blood-brain barrier
Syndromes
Nursing models
Neurological disorders
Sequence analysis
Cerebral circulation
Inflammation
Carotid artery stenosis
Western immunoblotting
Immunohistochemistry
Health outcome assessment
Magnetic resonance imaging
White matter (Nerve tissue)
Randomized controlled trials
Oxidative stress
Cytochemistry
Cellular signal transduction
Gene expression
Drug synergism
Telencephalon
Fluorescent antibody technique
Gene expression profiling
Memory disorders
Descriptive statistics
Brain injuries
Vascular diseases
Inhalation administration
Neuroglia
Inflammatory mediators
Drug side effects
Polymerase chain reaction
Nanoparticles
Behavior modification
Evaluation
Zdroj: Environmental Health Perspectives. Aug2021, Vol. 129 Issue 8, p1-087006-18. 18p. 4 Color Photographs, 3 Diagrams, 1 Chart, 1 Graph.
Abstrakt: 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 =200 nm) 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. [ABSTRACT FROM AUTHOR]
Databáze: GreenFILE
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