How Your Brain Cleans Itself—Mystery Solved?

ORIGINAL: NatGeo

Dave Mosher for National Geographic News

August 16, 2012

Plumbing system found in mice makes scientist's "heart sing."

Tracer molecules (purple) reveal nerve cell pores drawing cerebrospinal fluid (green) across brain tissue. I mage courtesy J. Iliff and M. Nedergaard, AAAS

Green tracer molecules drift through cerebrospinal fluid crowding around a blood vessel. Image courtesy J. Iliff and M. Nedergaard, AAAS

Talk about brainwashing—a newfound plumbing system, identified in mice, likely helps the brain empty its waste, a new study says. Because mouse biology is similar to ours, the same findings should apply to people too, experts say.

Thanks to a blood-brain barrier—a natural wall that protects the brain tissue—the organ never touches blood, thus protecting it from microbes, viruses, and other pathogens.

To get nutrients to brain tissue and remove its waste, the brain makes a liquid called cerebrospinal fluid. But exactly how the fluid removes gunk generated by brain cells wasn't certain until now.

Experiments in the 1950s and '60s hinted that diffusion—the passive method by which, say, food coloring spreads out in a glass of water—moved cerebrospinal fluid around the brain.

Yet this process is too slow to explain the brain's lightning-fast activity and immaculate cleanliness.

It turns out that, while studying brain tissue, the researchers in the 1950s and '60s unwittingly turned off the plumbing that washes the tissue.

"The idea of a cleaning system based on pressure has been around for a long time, but if you open the skull anywhere, like a hydraulic pump, it stops. They thought [the cleaning system] didn't exist," said study leader Maiken Nedergaard, a neuroscientist at the University of Rochester Medical Center.

The pump system is "on the order of a thousand times faster than diffusion," she said. "I'm surprised that no one had discovered this until now."

(Read "Beyond the Brain" in National Geographic magazine.)

Brain Under Pressure

Nedergaard and her colleagues dubbed the newfound plumbing the glymphatic system, after neural tissue called glial cells, which power the flow of cerebrospinal fluid.

Glial cells do this by growing their "feet" around vessels and veins that carry blood, forming a sort of pipe around a pipe.

Tiny pores in this outer pipe then suck nutrient-rich cerebrospinal fluid from the blood vessels into channels dense with nerve cells, and pores at other locations pump the fluid out. The process simultaneously carries away the brain's waste while feeding its cells.

Nedergaard and her team used a special two-photon microscope, whose infrared light allows a deep, clear look into living brain tissue without harming it.

"These microscopes are revolutionizing neuroscience, and they've only become commercially available in the past five or six years," Nedergaard said.

Studying living mouse brains required opening their skulls. Yet unlike in previous experiments, the researchers sealed each hole with a tiny glass plate, keeping the fluid pressure while providing a window for the microscope.

Fluorescent dyes injected into the mouse brains then allowed the team to record movies of the cerebrospinal fluid moving through brain tissue.

"The fact we could look at it and make a movie was very important to showing the flow," Nedergaard said.

(See brain pictures.)

Brain Study Makes Scientist's "Heart Sing"

Clinical neuroscientist Bruce Ransom, who studies glial cells but was not involved in the study, said the work makes his "heart sing."

"It wasn't impossible to imagine that cerebrospinal fluid moves with enough force to be a garbage-disposal system, but that was always speculative," said Ransom, of the University of Seattle.

"This team, however, has done something very clever to find this system: demonstrate how it works and show it can vigorously wash away waste."

Now that the plumbing has been found, study leader Nedergaard and her colleagues are exploring its implications. A big one may be in its role in Alzheimer's disease, which is thought to arise when brain cells are killed by the accumulation of a protein waste called beta-amyloid.

"Next we need to move beyond mice," Nedergaard said. "We need to see if this same system exists in humans—which I suspect it does."

The study of the brain's plumbing system was published in the journal Science Translational Medicine.