Scientists find a way to restore the brain’s self-cleaning function

Alzheimer’s, Parkinson’s and other neurological disorders can be considered “dirty brain” diseases, where the brain has difficulty eliminating harmful waste. Age is a major risk factor because our brain’s ability to eliminate toxic buildup declines as we age. However, new research in mice shows that it is possible to reverse age-related effects and restore the brain’s waste elimination process.

“This research shows that restoring cervical lymphatic function can significantly prevent the age-related slowing of waste removal from the brain. Moreover, this was achieved with a drug that is already in clinical use and offers a potential treatment strategy.”

Douglas Kelley, PhD, Professor of Mechanical Engineering, Hajim School of Engineering and Applied Sciences, University of Rochester

Kelley is one of the lead authors of the study, which was published in the journal Natural Aging, together with Maiken Nedergaard, MD, DMSc, co-director of the university’s Center for Translational Neuromedicine.

First described by Nedergaard and her colleagues in 2012, the glymphatic system is the brain’s unique waste-elimination process that uses cerebrospinal fluid (CSF) to flush out excess proteins produced by energy-hungry neurons and other cells in the brain during normal activity. This discovery pointed the way to potential new approaches to treating diseases commonly associated with the buildup of protein waste in the brain, such as Alzheimer’s (beta-amyloid and tau) and Parkinson’s (alpha-synuclein). In healthy and young brains, the glymphatic system does a good job of flushing out these toxic proteins, but as we age, this system slows down, setting the stage for these diseases.

A network of tiny pumps sucks waste products out of the brain

Once inside the skull, the protein-waste-laden cerebrospinal fluid makes its way to the lymphatic system and eventually to the kidneys, where it is processed along with the body’s other waste. The new research combines advanced imaging and particle tracking techniques to detail for the first time the route, via the cervical lymph vessels in the neck, by which half of the dirty cerebrospinal fluid leaves the brain.

In addition to measuring CSF flow, the researchers were also able to observe and record the pulsation of the lymph vessels in the neck that help pump CSF out of the brain. “Unlike the cardiovascular system, which has one large pump, the heart, the fluid in the lymphatic system is instead transported by a network of tiny pumps,” Kelley said. These microscopic pumps, called lymphangions, have valves that prevent backflow and are lined up one after the other to form lymph vessels.

The researchers found that as the mice aged, the frequency of contractions decreased and the valves failed. As a result, the rate of dirty cerebrospinal fluid draining from the brains of older mice was 63 percent slower than in younger animals.

Well-known drug restarts the flow of brain cleansing fluid

The team then wanted to see if they could revive the lymphangions. They came across a drug called prostaglandin F2α, a hormone-like compound often used in medicine to induce labor that promotes smooth muscle contractions. The lymphangions are lined with smooth muscle cells. When the researchers applied the drug to the cervical lymph vessels of older mice, both the frequency of contractions and the drainage of dirty cerebrospinal fluid from the brain increased, returning to the levels of efficiency seen in younger mice.

“These vessels are conveniently located near the surface of the skin, we know they are important, and we now know how to accelerate their function,” Kelley said. “You can see how this approach, perhaps in combination with other interventions, could be the basis for future therapies for these diseases.”