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.
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 rolein Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and other neurodegenerative illnesses, research suggests. “This is a revolutionary finding,” Nedergaard says. “This system plays a huge role in the health of the brain.”
Nedergaard describes the glymphatic system as like a dishwasher for the brain. “The brain is very active,” she says, “and so it produces a lot of junk that needs to be cleaned out.”
In hindsight, she says, the system should have been noticed long ago. When the skull and head are dissected, the vessels are visible to the naked eye. But no one bothered to really look: “Usually the brain is seen only as a bunch of nerve cells. We have come to think of the brain as a computer. And it’s not. It’s a living organ.”
Nedergaard and Benveniste 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. The reason for these differences remains unclear, but Nedergaard suspects that it is probably related to the mechanical engineering of the lymphatic vessels and valves; she suggests that the healthiest approach may be to move periodically while you sleep.
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 acidsimproved glymphatic functioning.
Terminally differentiated lymphatic vessels in the dura mater of the brain.
The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.