The brain and the lymphatic system have always been known as exclusive to each other. In other words, the lymphatic system, critical to carrying immune cells and removing wastes from the body, stopped at the brain.
But recent research from Finland involving glowing mouse heads (yes, you read that correctly) has altered this long-held notion.
Three years ago, Kari Alitalo, a scientist at the University of Helsinki, wanted to develop a more precise map of the lymphatic system. To do this, he used genetically modified mice whose lymphatic vessels glowed when illuminated by a particular wavelength of light. (The mice had been given a gene from a species of glowing jellyfish.)
When viewing the modified mice under the light, Aleksanteri Aspelund, a medical student in Alitalo’s laboratory, saw something unexpected: The heads of the mice glowed. At first, he suspected that there was something wrong — with the animals, the lighting or the measuring equipment. But when Alitalo and Aspelund repeated the experiment, they got the same result. It seemed that the lymphatic vessels extended to the brain after all.
The discovery is much more than a historical footnote. It has major implications for a wide variety of brain diseases, including Alzheimer’s, multiple sclerosis, stroke and traumatic brain injury.
Researchers have identified two networks: the vessels that lead into and surround the brain, and those within the brain itself. The first is known as the lymphatic system for the brain, while the latter is called the glymphatic system. The “g” added to “lymphatic” refers to glia, the kind of neuron that makes up the lymphatic vessels in the brain. The glymphatic vessels carry cerebrospinal fluid and immune cells into the brain and remove cellular trash from it. One scientist described the glymphatic system as “a dishwasher for the brain.”
Could a Malfunctioning Lymphatic System Promote Alzheimer’s?
Alitalo and others have found evidence that when the systems malfunction, the brain can become clogged with toxins and suffused with inflammatory immune cells. Over decades, this process may play a key role in Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and other neurodegenerative illnesses.
Scientists at Yale University, have found evidence linking problems in the lymphatic and glymphatic systems to Alzheimer’s. In a study on mice, they showed that glymphatic dysfunction contributes to the buildup in the brain of amyloid beta, a protein that plays a key role in the disease.
Last year, Jeff Iliff, a neuroscientist at Oregon Health & Science University, and several colleagues examined postmortem tissue from 79 human brains. They focused on aquaporin-4, a key protein inglymphatic vessels. In the brains of people with Alzheimer’s, this protein was jumbled; in those without the disease, the protein was well organized. This suggests that glymphatic breakdowns may play a role in the disease, Iliff says.
Recent research has also found evidence that the glymphatic system may extend into the eye. For decades, scientists have noted that many people with Alzheimer’s disease also have glaucoma, in which damage to the optic nerve causes vision loss. But they struggled to find a common mechanism; the glymphatic system may be the link.
In January, Belgian and Swiss researchers identified a rich network of glymphatic vessels within the optic nerve. The scientists also found that when these vessels malfunction, they seem to leave behind deposits of amyloid beta as well as other neurotoxins that damage the optic nerve.
How Sleep and Sleep Position Clear the Brain
One key to glymphatic performance seems to be sleep. In mice, the system processes twice as much fluid during sleep as it does during wakefulness. In studies, the lymphatic system removed much more of the protein when the animals were asleep than when they were awake. The lead scientist suggests that over time, sleep dysfunction may contribute to Alzheimer’s and perhaps other brain illnesses. “You only clean your brain when you’re sleeping,” she says. “This is probably an important reason that we sleep. You need time off from consciousness to do the housekeeping.”
The same researchers have also found that sleep position is crucial. In an upright position — someone who is sitting or standing — waste is removed much less efficiently. Sleeping on your stomach is also not very effective; sleeping on your back is somewhat better, while lying on your side appears to produce the best results.
Sleep is probably not the only way to improve glymphatic flow. For instance, a paper published in January by Chinese researchers reported that in mice, omega-3 fatty acids improved glymphatic functioning. And in a small human study, other scientists have found that deep breathing significantly increases the glymphatic transport of cerebrospinal fluid into the brain.
Alitalo is experimenting with growth factors, compounds that can foster regrowth of the vessels in and around the brain. He has used this method to repair lymphatic vessels in pigs and is now testing the approach in the brains of mice that have a version of Alzheimer’s.
“Right now there are no clinical therapies in this area,” he says. “But give it a little time. This has only just been discovered.”
To read more and reference the studies, go here: