Conduit to the Brain: Particles enter the nervous system via the nose

Like stealthy intruders, minute airborne particles can apparently invade the brain through a vulnerable portal. At least some such particles, when inhaled into the nose, shimmy up the nerve bundle that governs smell and infiltrate the central nervous system, bypassing the natural firewall between brain tissue and the main circulatory system, new research suggests.

That has both worrisome and promising implications, according to scientists. For one thing, particulate matter from human activities such as burning of diesel fuel may cause neurological problems in addition to harming the heart and lungs.

On the other hand, aerosolized particles that circumvent the blood-brain barrier might someday serve as delivery vehicles for drugs.

The brain’s barrier blocks most dangerous foreign particles, such as pathogens. Evidence that certain particles in the nose can circumvent that barrier cropped up as early as 1941, but little research followed, says Günter Oberdörster of the University of Rochester in New York.

He and his colleagues placed a dozen rats for 6 hours in a chamber containing airborne particles made up of carbon-13 no more than 100 nanometers across. At 1, 3, 5, and 7 days after the exposure, the scientists removed and examined some of the animals’ lungs and parts of their brains.

Compared with tissues from rats that hadn’t breathed the particles, the animals’ lungs 1 day after exposure contained an average excess of 1.39 micrograms of carbon-13 per gram of tissue, and their brains’ olfactory bulbs showed an excess of 0.35 g/g.

Excess carbon in the lungs declined over the course of a week to 0.59 g/g, but concentrations in the olfactory bulbs continued to rise, reaching 0.43 g/g a week after exposure. Other brain areas also contained excess carbon in the exposed animals after 1 day but not consistently thereafter, the team reports in an upcoming Inhalation Toxicology.

The immune system gradually removes small foreign debris from the lungs, earlier studies have indicated. The new research hints that particles can become more permanently lodged in the brain. This could permit minute particles to accumulate with potentially toxic consequences.

Of greatest concern are combustion by-products, to which people experience lifelong exposure, says chemist Vicki Colvin of Rice University in Houston, who studies nanomaterials for potential health and environmental effects (SN: 3/30/02, p. 200: Taming High-Tech Particles). People are much more likely to inhale dangerous amounts of such mundane pollutants than to breathe in substantial quantities of ultrafine engineered materials, Colvin says. But in light of the new results, high-tech materials such as carbon nanotubes should also be investigated for possible neurotoxic effects, she adds.

The “paucity of toxicological data” on engineered nanoparticles mandates a “focus on safety testing,” says toxicologist David B. Warheit of DuPont Haskell Laboratory in Newark, Del.

Both Colvin and Warheit express hope that scientists might exploit the new findings to deliver drugs directly to the brain. Colvin suggests, for example, that nanoparticles containing therapeutic compounds might be inhaled as treatment for people with Parkinson’s disease.


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