In 2015, Researchers discovered new information about the body’s lymphatic system. In fact, they found newly discovered vessels that directly connect the lymphatic system to the brain. Researchers from the University of Virginia published their findings in Nature.
Many scientists previously argued these vessels didn’t exist. Now, the new information alters what we understand about diseases like multiple sclerosis, autism, and Alzheimer’s.
“The first time these guys showed me the basic result, I just said one sentence: ‘They’ll have to change the textbooks,” said Kevin Lee, Ph.D., chairman of the UVA Department of Neuroscience. “There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation – and they’ve done many studies since then to bolster the finding – that it will fundamentally change the way people look at the central nervous system’s relationship with the immune system.”
This amazing discovery means that textbooks will need to be rewritten. It is difficult to understand how these vessels escaped detection when scientists have thoroughly mapped them throughout the body. The most important result of this discovery will be the innovations in the study and treatment of neurological diseases.
“Instead of asking, ‘How do we study the immune response of the brain?’ ‘Why do multiple sclerosis patients have the immune attacks?’ Now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels,” said Jonathan Kipnis, Ph.D., professor in the UVA Department of Neuroscience and director of UVA’s Center for Brain Immunology and Glia (BIG). “It changes entirely the way we perceive the neuroimmune interaction. We always perceived it before as something esoteric that can’t be studied. But now we can ask mechanistic questions.”
“We believe that for every neurological disease that has an immune component to it, these vessels may play a major role,” Kipnis said. “Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component.”
Even Kipnis was skeptical initially. “I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped,” he said. “I thought that these discoveries ended somewhere around the middle of the last century. But apparently, they have not.”
Antoine Louveau, Ph.D., a postdoctoral fellow in Kipnis’ lab made the discovery. Louveau developed a method to mount a mouse’s meninges (membranes covering the brain) to a single slide to be examined.
“It was fairly easy, actually,” he said. “There was one trick: We fixed the meninges within the skullcap so that the tissue is secured in its physiological condition, and then we dissected it. If we had done it the other way around, it wouldn’t have worked.”
After pinpointing vessel-like patterns in the distribution of immune cells on those slides, he tested for lymphatic vessels and identified them. He spoke about the moment he found them. “I called Jony [Kipnis] to the microscope and I said, ‘I think we have something.’”
Kipnis described the brain’s lymphatic vessels as “very well hidden,” which is how they remained undetected for so long. The vessels follow a major blood vessel down into the sinuses, which is a difficult area to image.
“It’s so close to the blood vessel, you just miss it,” he said. “If you don’t know what you’re after, you just miss it.” “Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris,” Kipnis noted. Harris is a Ph.D., assistant professor of neuroscience, and member of the BIG center. Research associate, Igor Smirnov, also participated and has been recognized for his excellent surgical skills.
This discovery opens the door to new research involving the workings of the brain, diseases of the brain, and these new lymphatic vessels. For instance, in Alzheimer’s, big protein chunks accumulate in the brain. They may be accumulating due to the malfunctioning of these lymphatic vessels failing to remove the protein chunks. The vessels appear to change with age, so they may play a role in aging, which will likely be studied as well.