The central nervous system (CNS) controls most functions of the body and mind. It consists of two parts: the brain and the spinal cord. The brain is the center of our thoughts, the interpreter of our external environment, and the origin of control over body movement. Like a central computer, it interprets information from our eyes (sight), ears (sound), nose (smell), tongue (taste), and skin (touch), as well as from internal organs such as the stomach. The spinal cord is the highway for communication between the body and the brain.
The CNS is functionally connected to the immune system — the system that defends us against infectious organisms and other invaders. These two systems interact with each other on the basis of complex mechanisms that require the participation of immune cells and fluids containing soluble immune mediators — both of which need to access the CNS and operate within it.
The immune system uses lymphatic vessels to exchange immune cells and soluble mediators with tissues and organs, but the CNS does not contain lymphatic vessels. Or, does it?
Here are a few notable examples that illustrate the current view — or, as we will see, an outdated view — on the presence of lymphatic vessels in the CNS. “Lymphatic vessels are not found in CNS tissue”, states an article published in 2003 in Nature Review Immunology. According to an article that appeared in the scientific journal Immunological Reviews in 2006: “It is an undisputed anatomical fact that the CNS lacks a traditional lymphatic system.” A similar statement related to the CNS — “the lack of an obvious lymphatic system” — is present in an article published in 2010 in the Journal of Clinical Investigation. Even a very recent (February 2015) article published in the journal Brain, Behavior, and Immunity, states that “the CNS does not have a well-developed lymphatic system.”
Interestingly, the review authors do not corroborate their statements with references to experimental evidence showing that lymphatic vessels are not present in the CNS. Rather, these statements appear based on “accepted views.” It seems, once again, an instance of the favorite “there is no evidence to show…..”, when the evidence has not been accurately researched. In other words, there is no evidence because no one has been looking — at least systematically — for that evidence. Finally, someone — serendipitously — found the evidence (against the evidence): experimental results published in the journal Nature (June 1, 2015) show that the CNS is directly connected to the immune system by lymphatic vessels previously thought not to exist.
Antoine Louveau, a postdoctoral fellow in the lab of Jonathan Kipnis at the University of Virginia School of Medicine, developed a method to mount a mouse’s meninges — the membranes covering the brain — on a single slide. Thus, the meninges could be examined as a whole. He noticed that immune cells were distributed in vessel-like patterns. Thus, he tested for lymphatic vessels, and he found them. The vessels are able to carry both fluid and immune cells, and are connected to the deep cervical lymph nodes.
So, why were these lymphatic vessels missed by previous investigators? In a press release, Kipnis said that they are “very well hidden” and noted that they follow a major blood vessel down into the sinuses, an area difficult 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.”
In their paper, the researchers conclude that “Malfunction of the meningeal lymphatic vessels could be a root cause of a variety of neurological disorders in which altered immunity is a fundamental player such as multiple sclerosis, Alzheimer’s disease, and some forms of primary lymphoedema that are associated with neurological disorders.”
Kipnis said in the press release: “In Alzheimer’s, there are accumulations of big protein chunks in the brain. We think they may be accumulating in the brain because they’re not being efficiently removed by these vessels.” Other neurological diseases, from autism to multiple sclerosis, should be reconsidered in light of the presence of something science insisted did not exist.
In addition, Kipnis told The Scientist that, at the very least, these latest results add to mounting evidence of immune activity in the healthy brain. “If you go into the literature, 20 years ago, the idea was that if you see immune cells in the brain, something must be going wrong. Now we know that we see immune cells in healthy brains. . . . It’s part of normal physiology; it should be there. Immune activity in the brain is not always pathological.”
Obviously, the new discovery will point to numerous new avenues of research. However, one of the most important unanswered questions at this time is: “Do these CNS lymphatic vessels exist in humans?”