A new study has described for the first time a detailed pathway through the cervical lymphatic vessels in the neck that drains half of the waste-laden cerebrospinal fluid from the brain.
When the CSF becomes filled with protein waste, the fluid in the skull needs to reach the lymphatic system and eventually travel to the kidneys, where it is processed along with other body waste.
The new study combined advanced imaging and particle tracking techniques to reveal this pathway.
“Dirty brain diseases”
Alzheimer’s, Parkinson’s, and other neurological disorders can be considered “dirty brain diseases,” where the brain struggles to get rid of harmful waste.
Aging is a major risk factor for these diseases because the brain’s ability to remove toxic buildup slows as we age.
However, new research in mice has shown that it is possible to reverse the effects of aging and restore the brain’s waste-cleaning process.
“This study shows that restoring the function of the cervical lymphatic vessels can significantly rescue the age-related slowing of waste removal from the brain,” said Douglas Kelly, a professor of mechanical engineering at the University of Rochester’s School of Engineering and Applied Sciences and one of the study’s lead authors.
“Moreover, this was achieved using a drug that is already in clinical use, providing a potential therapeutic strategy,” Kelly added.
The results of the study, which Kelly worked on, were published in the journal Nature Aging, along with Maiken Nedergaard, MD, PhD, co-director of the Center for Translational Medicine at the University of Rochester in the United States of America.
Waste removal system
The glymphatic system was first described by Nedergaard and colleagues in 2012. Given that the system relies on water flow from glial cells, a type of cell found in the nervous system, and has a lymphatic function in filtering solutes between cells, the researchers proposed that this system be called the “glymphatic” pathway.
This is a unique process for removing waste from the brain and uses cerebrospinal fluid to wash away excess proteins generated by neurons and other particles in the brain during normal activity.
These findings point to potential new therapeutic approaches for treating diseases associated with the accumulation of protein waste in the brain, such as Alzheimer’s (beta-amyloid and tau proteins) and Parkinson’s (alpha-synuclein protein).
The glymphatic system in healthy, young brains does a good job of getting rid of these toxic proteins, but as we age, this system slows down, setting the stage for these diseases to develop.
small pumps
The researchers were able to measure the flow of cerebrospinal fluid, and monitor and record the pulsations of the lymphatic vessels in the neck that help drain cerebrospinal fluid from the brain.
“Unlike the cardiovascular system, which has one large pump, the heart, fluids in the lymphatic system are moved through a network of tiny pumps,” Kelly said, according to EurekAlert. These microscopic pumps, called lymphangions, have valves to prevent backflow, and some of them connect to form lymphatic vessels.
The researchers found that as the mice aged, the frequency of contractions decreased and the valves failed. As a result, the speed of waste-laden cerebrospinal fluid flowing out of the brains of older mice was 63 percent slower than that of younger mice.
well known medicine
The team then tried to see if they could revive the lymphangions and get them working again and found a drug called prostaglandin F2 alpha, a hormone-like compound used medically to induce labor, and known to help smooth muscle contract.
Lymphatic vessels are lined with smooth muscle cells, and when the researchers applied the drug to the cervical lymphatic vessels of older mice, the frequency of contractions and the flow of waste-laden cerebrospinal fluid from the brain increased, returning to the level of efficiency seen in younger mice.
“These vessels are conveniently located close to the surface of the skin, we know they are important, and now we know how to speed up their function,” Kelly said.
“One can see how this approach, perhaps in combination with other interventions, could be the basis for future treatments for these diseases,” he added.