MIND
August 17, 2012

Mind-Blowing, Literally

We thought we knew how the brain cleans itself out. Then a completely unexpected and very fast new cleaning system showed up.

Like any other organ, the brain has to clean itself out constantly. After all, accumulating debris can hamper the function of any organ, and, given the brain’s high-octane status, cleaning itself out is especially important. When debris (like protein) accumulates in the brain, diseases like Alzheimer’s can develop.

'It's as if the brain has two garbage haulers – a slow one that we've known about, and a fast one that we've just met.'

Researchers have known about one of the cleaning methods the brain uses: Cerebrospinal fluid (CSF) “percolates” throughout the brain by diffusion and filters out unwanted gunk. But now researchers have discovered a more active method of clearance, which they’ve named the “glymphatic” system, after the glial cells that are in charge of it.

It turns out that astrocytes, a type of glial cell, use their foot-like projections to construct a network of “plumbing” just outside the brain’s network of veins and arteries. The team describes the newly discovered network like a canopy of branches forming a tunnel adjacent to or on top of the road below. Cerebrospinal fluid is pumped through this tunnel by “convection” or “bulk flow” – a much more powerful flow than was previously known.

"It's as if the brain has two garbage haulers – a slow one that we've known about, and a fast one that we've just met," said Maiken Nedergaard, senior author of the study. "Given the high rate of metabolism in the brain, and its exquisite sensitivity, it's not surprising that its mechanisms to rid itself of waste are more specialized and extensive than previously realized." Because of the delicacy of the system, it typically deteriorates once the brain dies, which is why researchers had not visualized it till now. Nedergaard and colleagues used a highly sensitive microscopy method on the living mouse brain to observe this new hydraulic network in action.

“We're hopeful that these findings have implications for many conditions that involve the brain, such as traumatic brain injury, Alzheimer's disease, stroke, and Parkinson's disease," said Nedergaard. For example, it’s believed that Alzheimer’s disease occurs because the brain is no longer able to clear amyloid-beta as it should, and accumulating protein is what leads to the cognitive problems that patients experience.

"If the glymphatic system fails to cleanse the brain as it is meant to, either as a consequence of normal aging, or in response to brain injury,” said study author Jeffrey Iliff, “waste may begin to accumulate in the brain. This may be what is happening with amyloid deposits in Alzheimer's disease.” Iliff also discovered that about half of the amyloid carried out of the brain was done through the glymphatic system.

How the results will help in the development of more successful treatments for brain diseases remains to be seen, but they may lead to some possibilities, particularly since many brain diseases result from breakdown in the brain’s cleaning system. “Perhaps increasing the activity of the glymphatic system might help prevent amyloid deposition from building up,” said Iliff, “or could offer a new way to clean out buildups of the material in established Alzheimer's disease.”

The research was carried out at the University of Rochester Medical Center and published in Science Translational Medicine.

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