Orange color shows Inflammation response in the brain
Credit: Andrew Ottens, PhD, Virginia Commonwealth University

Recent headlines tell a disturbing story: people who are exposed to high levels of air pollution containing fine particulates face a markedly higher risk of developing degenerative neurological diseases like Alzheimer’s.

UNM scientist Matt Campen, PhD, thinks his research may hold a clue that explains the link between inhaled pollutants and neurological conditions.

In a new paper published in the Proceedings of the National Academy of Sciences, Campen and his colleagues report that tiny inhaled particles trapped in the lung trigger the release of inflammatory molecules that course through the circulatory system.

These molecules can open the blood-brain barrier, setting off a cascade of inflammation beyond the tiny blood vessels that nourish and protect brain tissue. Campen has also shown that fasudil, a Rho kinase inhibitor that prevents this blood-brain barrier disruption, can stave off neural inflammation.

There is concern that inhaled particles may eventually travel directly to the brain.

“The lungs don't hate you,” notes Campen, a professor in the pharmaceutical sciences department in the UNM College of Pharmacy. “They exist for your protection.” Inhaled particles irritate lung tissue, he says, triggering the secretion of inflammatory proteins as a protective response. Thus, the particles do not have to leave the lung to cause effects in the brain.

In his research Campen exposed mice to multi-walled carbon nanotubes, tiny particles that are frequently used in manufacturing due to their unique properties, when they infiltrate lung tissue, Campen says, “You get spillover of signaling molecules in the blood. They travel to the brain and open the endothelial barrier.”

In effect, the inflammatory molecules released by the lungs come into contact with the lining of the blood vessels in the brain, loosening the tightly bonded cells that form the blood-brain barrier (which normally protect the brain from infections and toxins).

These inflammatory molecules infiltrate the microglia and astrocytes that surround and support the neurons in the brain, Campen says. “Microglia, astrocytes – they’re supposed to help the neurons do their thing - learning, thinking, processing," he says. “When you distract them with these environmental exposures, they can’t do their work.”

Campen’s research was conducted with colleagues from Virginia Commonwealth University and the National Institute for Occupational Safety and Health. It complements a study published last month in Translational Psychiatry by a University of Southern California team, which found that chronic exposure to fine particulates accelerated signs of brain aging in people with a genetic predisposition to develop Alzheimer’s disease.

Other research has also tied air pollution to autism and other diseases that affect learning and memory, Campen says. But the link with the cardiovascular system suggests therapies that might be effective in treating these problems, he says.

“We know it’s getting to the blood vessels, and blood vessels are in every organ,” he says, “So let’s start there to target these neurological outcomes.”