Particles Transported to the Brain

The Polluted Brain is Under Intense Study

From an Article by Emily Underwood, Science Magazine, January 26, 2017

Los Angeles, CA—In a barbed wire–enclosed parking lot 100 meters downwind of the Route 110 freeway, an aluminum hose sticks out of a white trailer, its nozzle aimed at an overpass. Every minute, the hose sucks up hundreds of liters of air mixed with exhaust from the roughly 300,000 cars and diesel-burning freight trucks that rumble by each day.

Crouched inside the trailer, a young chemical engineer named Arian Saffari lifts the lid off a sooty cylinder attached to the hose, part of a sophisticated filtration system that captures and sorts pollutants by size. Inside is a scientific payload: particles of sulfate, nitrate, ammonium, black carbon, and heavy metal at least 200 times smaller than the width of a human hair.

The particles are too fine for many air pollution sensors to accurately measure, says Saffari, who works in a lab led by Constantinos Sioutas at the University of Southern California (USC) here. Typically smaller than 0.2 µm in diameter, these “ultrafine” particles fall within a broader class of air pollutants commonly referred to as PM2.5 because of their size, 2.5 µm or less. When it comes to toxicity, size matters: The smaller the particles that cells are exposed to, Saffari says, the higher their levels of oxidative stress, marked by the production of chemically reactive molecules such as peroxides, which can damage DNA and other cellular structures.

Some of the health risks of inhaling fine and ultrafine particles are well-established, such as asthma, lung cancer, and, most recently, heart disease. But a growing body of evidence suggests that exposure can also harm the brain, accelerating cognitive aging, and may even increase risk of Alzheimer’s disease and other forms of dementia.

The link between air pollution and dementia remains controversial—even its proponents warn that more research is needed to confirm a causal connection and work out just how the particles might enter the brain and make mischief there.

But a growing number of epidemiological studies from around the world, new findings from animal models and human brain imaging studies, and increasingly sophisticated techniques for modeling PM2.5 exposures have raised alarms. Indeed, in an 11-year epidemiological study to be published next week in Translational Psychiatry, USC researchers will report that living in places with PM2.5 exposures higher than the Environmental Protection Agency’s (EPA’s) standard of 12 µg/m³ nearly doubled dementia risk in older women.

If the finding holds up in the general population, air pollution could account for roughly 21% of dementia cases worldwide, says the study’s senior author, epidemiologist Jiu-Chiuan Chen of the Keck School of Medicine at USC.

Deepening the concerns, this month researchers at the University of Toronto in Canada reported in The Lancet that among 6.6 million people in the province of Ontario, those living within 50 meters of a major road—where levels of fine pollutants are often 10 times higher than just 150 meters away—were 12% more likely to develop dementia than people living more than 200 meters away.

The field is “very, very young,” cautions Michelle Block, a neuroscientist at Indiana University in Indianapolis. Nonetheless, it’s a “hugely exciting time” to study the connections between pollution and the brain, she says. And if real, the air pollution connection would give public health experts a tool for sharply lowering Alzheimer’s risks—a welcome prospect for a disease that is so devastating and that, for now, remains untreatable.

Demented dogs in Mexico City in the early 2000s offered the first hints that inhaling polluted air can cause neurodegeneration. Neuroscientist Lilian Calderón-Garcidueñas, now at the University of Montana in Missoula, noticed that aging dogs who lived in particularly polluted areas of the city often became addled, growing disoriented and even losing the ability to recognize their owners. When the dogs died, Calderón-Garcidueñas found that their brains had more extensive extracellular deposits of the protein amyloid b—the same “plaques” associated with Alzheimer’s disease—than dogs in less polluted cities.

She went on to find similarly elevated plaque levels in the brains of children and young adults from Mexico City who had died in accidents, as well as signs of inflammation such as hyperactive glia, the brain’s immune cells. Calderón-Garcidueñas’s studies didn’t have rigorous controls, or account for the fact that amyloid b plaques don’t necessarily signal dementia. But later work lent weight to her observations.

Those tubes of fine particles from the Route 110 freeway have played a key role. In a basement lab at USC, Sioutas and his team aerosolize the pollutants with a hospital nebulizer, then pipe the dirty air into the cages housing lab mice that have been engineered to contain a gene for human amyloid b. Control animals housed in the same room breathe clean, filtered air. After a designated period—220 hours over several weeks, in a recent experiment—the team hands the rodents over to colleagues at USC, who kill the animals and check their brains for signs of neuro-degeneration.

Caleb Finch and Todd Morgan, USC neuroscientists who combine studies of aging and the brain, are in charge of the analysis. In mice that breathed the dirty air, they have found, the brain’s microglia release a flood of inflammatory molecules, including tumor necrosis factor a, which is elevated in the brains of people with Alzheimer’s disease and has been linked to memory loss. The pollution-exposed mice also showed other signs of brain damage, the group has reported in several recent papers: more amyloid b than in the control mice and shrunken and atrophied neurites, the cellular processes that extend from neurons toward other cells.

Just how the fine airborne particles might travel from a rodent’s nasal cavity to its brain is a mystery. But a research team led by Günter Oberdörster at the University of Rochester in New York has used traceable, radioactive specks of elemental carbon to demonstrate that inhaled particles smaller than 200 nanometers can get through the delicate tissues lining a rodent’s nasal cavities, travel along neurons, and spread as far as the cerebellum, at the back of the brain, triggering an inflammatory reaction.

To understand what the animal studies might mean for people, however, scientists need to correlate air pollution exposure with human brain scans and with results from rigorous cognitive testing.

That’s not easy to do, as long-term, historical data on pollution exposures are scarce in the United States and many other countries, says Kimberly Gray, a program administrator at the National Institute of Environmental Health Sciences (NIEHS) in Durham, North Carolina.

But in a September 2016 review of 18 epidemiological studies from Taiwan, Sweden, Germany, China, the United Kingdom, and the United States, all but one showed an association between high exposure to at least one component of air pollution and a sign of dementia. The review, published in Neurotoxicology, included a 2012 analysis of 19,000 retired U.S. nurses, which found that the more fine particulates the nurses were exposed to, based on monitoring data near their homes, the faster they declined on cognitive tests. For every additional 10 micrograms per cubic meter of air they breathed, their performance on tests of memory and attention declined as if they had aged by 2 years, says Jennifer Weuve, an epidemiologist at Boston University, who led the analysis.

Imaging studies also suggest that pollution attacks the human brain. In a 2015 analysis of brain MRI scans of people enrolled in the Framingham Heart Study, a long-term cardiovascular study in New England, researchers at Harvard Medical School in Boston found that the closer people had lived to a major roadway—and thus the more PM2.5 they had likely been exposed to—the smaller their cerebral brain volume. The association held up even after adjusting for factors such as education, smoking, diabetes, and cardiovascular disease.

Shortly after that study was published, USC’s Chen reported another example of brain shrinkage: In 1403 elderly women, the total volume of white matter—the insulated nerve fibers that connect different brain regions—decreased by about 6 cubic centimeters for every 3.5-µg/m³ increase in estimated PM2.5 exposure, based on air monitoring data from participants’ residences for 6 to 7 years before the brain scans were taken. Chen’s white matter findings are consistent with studies of cultured neurons, which show that exposure to PM2.5 can cause myelin—the fatty insulation that wraps around neuronal axons—to “peel up at the ends, like a Band-Aid,” Block says.

I think [air pollution] will turn out to be just the same as tobacco—there’s no safe threshold, said Caleb Finch, University of Southern California.

See also: www.FrackCheckWV.net

Examples of Ultrafine Dust Particles

WVU Researcher Warns About Toxic Ultrafine Dust in West Virginia

From an Article by Glynis Board, WV Public Broadcasting, April 15, 2015

When we hear about the danger of dust exposure, we are usually talking about coal dust underground, or silica dust. But that’s not the only dust that can make people sick. Apparently almost any dust can, if it’s fine enough.

Much research has surfaced over the past decade demonstrating clearer and clearer evidence that surface mining creates environmental hazards for communities in the vicinity. Epidemiologist Michael Hendryx has published a lot of research that demonstrates how life expectancy in the southern coalfields, for example, is much shorter than just about anywhere else in the country. But Michael McCawley says that’s not all we know.

“We also know they have a much increased rate of lung disease and also death from lung disease, much higher than in the rest of Appalachia and much higher than in the rest of the country in general.”

Michael McCawley is Interim Chair of the Department of Occupational and Environmental Health Sciences at West Virginia University. He’s been studying some aspects of air pollution that might shed new light on some of the human health disparities that seem to be abundant around surface mining operations, including lung and cardiovascular disease, and high blood pressure. His passion these days: ultrafine particle pollution.

Health Effects

By ultrafine, we are talking about dust small enough to pass right into the smallest parts of you.

“So your cell is kind of like Jell-O with a harder outside casing but the harder outside casing has pinholes,” McCawley explained, “and these particles are smaller than the pinholes. So they can move into the inside of the cell where the exposure results in inflammation. And inflammation is the beginning of a huge number of diseases.”

McCawley explains that there is a substantial body of literature that demonstrates the toxic effects of these particles. He says exposure to ultrafine particles emitted from diesel engines in Europe is associated with exacerbated asthma in young children as well as lung and cardiovascular diseases.

“They get into the lungs. In the lungs they can affect the nervous system. And the nervous system has an effect on the entire body including the arteries in the body. So you can get an increased blood pressure due to exposure just in the lungs.”

McCawley says it matters to some degree what the dust is made from, but all ultrafine particles are probably toxic.

“One of the ways we know that,” McCawley said, “they’ve done experiments with titanium dioxide. Titanium dioxide is the white pigment in paint. Generally it’s known to be fairly nontoxic.”

He says rats exposed to high concentrations of titanium dioxide dust at two, to four micrometers in size, has no effect on the animals’ health. But the same amount of exposure to ultrafine particles of titanium dioxide kills the rats.

Monitoring Ultrafine Particles

McCawley has been studying ultrafine particles in regions of West Virginia where surface mining is underway. In his research, he uses particle counters that indicate how many dust particles exist in the air. He has also been able to determine the sizes and distribution of particles. It’s a complicated metric system but McCawley says it provides much more accurate ideas of the doses of dust likely to be absorbed in human lungs.

He also looked at the makeup of the dust and was able to determine that it was, “crustal, in other words from dirt being disturbed,” McCawley said. “So that suggested to us that there was activity going on removing dirt and materials that would have aerosolized these crustal particles, so we assumed that would be associated with the mining activities.”

The Environmental Protection Agency does not have any rules on the books regulating ultrafine particle pollution. Rules do exist pertaining to larger dust particle exposure. But McCawley explains that EPA considers the overall mass of dust in the air for those rules. Ultrafine particles, he says, would need to be monitored and regulated differently.

McCawley recently gave a talk about ultra-fine particles to the Kanawha Forest Coalition, a group of Kanawha County residents concerned about a mountaintop removal site located near Charleston. He recommends that any community in the vicinity of surface mining or mountaintop removal test for ultrafine particle pollution.

But coal mining isn’t the only industry McCawley is concerned about. He says anywhere where there’s a lot of traffic or diesel generators (highways and horizontal gas drilling operations, for example) are major sources of ultrafine particle pollution. McCawley is also set to talk in Doddridge County, April 16th at 6 pm, at the Senior Center in West Union, to folks who live in the heart of West Virginia’s natural gas boom.

See also: www.FrackCheckWV.net