Breaching the Barrier: Nanoscale Particulate Matter and Measures of Brain Health

Abstract

The association between air pollution and respiratory and cardiovascular disease is well established.1^,2 Although air pollution’s effects on tissues other than the heart and lungs may be less intuitive, mounting evidence suggests that sustained exposure to ambient pollutants may lead to neurological disorders.3 A new study published in Environmental Health Perspectives uses a mouse model of brain injury to examine the cumulative risk of traffic-related air pollution (TRAP) and preexisting neurological disease.4

TRAP exists as a cocktail of fine particulate matter (${\mathrm{PM}}_{2.5}$), noxious gases, and other substances deriving from vehicle exhaust and road and tire wear.5 Air pollution is a global health issue: 95% of the world’s population live in areas that fail to meet the World Health Organization’s Air Quality Guideline of $10\mathrm{\mu }{\mathrm{g}/\mathrm{m}}^3$ for ${\mathrm{PM}}_{2.5}$.6

Although once controversial,7^,8 the notion that airborne contaminants may affect the brain has gained traction within the research community. Troubling evidence first arose in the early 2000s, when researchers found hallmarks of inflammation and Alzheimer’s disease in the brains of stray dogs in Mexico City.9^,10 More recently, a review of epidemiological studies on air pollution and Alzheimer’s disease and related dementias reported that the evidence was strongest for ${\mathrm{PM}}_{2.5}$ and cognitive decline, although strong associations remain elusive for other end points in part due to methodological challenges.11 Several other studies have found associations between TRAP exposure and childhood behavioral and cognitive outcomes such as attention deficit/hyperactivity disorder, impaired memory, and changes in cognitive development.12^,13^,14

Air pollution cannot be the sole driver of neurological disorders, or these cases would be much more prevalent, suggests Lucio Costa, a professor in the Department of Environmental and Occupational Health Sciences at the University of Washington, who was not involved in the new study. “What is emerging is that there is a need for [both] exposure [and] interaction with a specific genetic background or predisposing disease,” he says.

The new study investigated the latter category. “Very few studies have looked at interactions between PM and underlying neurological diseases,” says the paper’s senior author, William Mack, a professor of neurological surgery and vice chair of academic affairs at the Keck School of Medicine, University of Southern California. To do this, the authors exposed mice for 6 weeks to either filtered air or PM collected from a Los Angeles freeway, then performed bilateral carotid artery stenosis (BCAS) to restrict blood flow to the brain. This procedure not only reduces oxygen supply to the brain but also weakens the blood–brain barrier and causes brain inflammation.4 After an additional 4 weeks of filtered air or PM exposure, they analyzed physiological, behavioral, biochemical, and histological data.

The researchers chose to study not ${\mathrm{PM}}_{2.5}$ but, rather, nanoscale PM (nPM), defined as particles $\le 200\mathrm{\hspace{0.17em}nm}$ in aerodynamic diameter. “The PM size was chosen due to the higher toxicity that … small particles have exhibited in vitro and in vivo,” Mack explains. “It is thought that these particles are more easily able to penetrate to the smallest airways in the lungs and affect the systemic circulation.”

A new in vitro study shows that nanoscale particles from traffic-related air pollution may cross the blood–brain barrier and act synergistically with underlying neurological disease to increase inflammation and oxidative stress in the brain. These two processes are involved in many neurodevelopmental and neurodegenerative diseases. Image: © Mitch Diamond/Getty Images.

Results showed that in the BCAS group exposed to nPM, adverse effects in white matter were synergistic rather than additive—the joint effect of exposure and pathology was greater than the sum of the two. The $\text{nPM\hspace{0.17em}}+\text{\hspace{0.17em}BCAS}$ exposure group experienced a 30% reduction in white matter volume, impaired working memory, and synergistic increases in inflammation and oxidative stress, compared with the group exposed to filtered air. Translated to human health, these findings suggest that individuals with underlying neurological conditions may be more vulnerable to neurotoxic exposures. According to the authors, the findings agreed with previous observations that inflammation and oxidative stress are fundamental to the brain’s response to TRAP exposure; whether this response is systemic, local, or a combination of both remains unclear, Mack says.

“There is a now a good convergence of findings from clinical, epidemiological, animal, and in vitro studies strongly suggesting that TRAP affects the brain via neuroinflammation and oxidative stress, two processes that are relevant for a number of neurodevelopmental and neurodegenerative diseases,” says Costa. This knowledge may lead to therapies, but scientists would also like to see it inform policy.

“This study represents a more realistic model of human risk conditions, providing the opportunity to identify mechanisms of convergence and to evaluate whether current regulations for air pollution are sufficiently protective when other vulnerability factors exist,” says Deborah Cory-Slechta, a professor of environmental medicine at the University of Rochester School of Medicine and Dentistry. Such models could also be useful for identifying individual contaminants responsible for air pollution’s adverse effects. “This is particularly important from a public health protection and prevention capacity,” Cory-Slechta says, “as it is possible to regulate levels of emission of those components.”

Biography

Florencia Pascual, PhD, is a science writer based in Durham, North Carolina.