Guess what. It may be time to throw out all our anatomy and physiology textbooks. You know, the ones we used in Med school, the ones I used to teach the next generation of health professionals at schools across this great nation. Because there’s been a new discovery- one that will affect how we think about the brain for a long time in the future.
I’m not sure this qualifies as serendipity. Thar was one of my favorite words that I learned some 60 years ago. It was first coined by Horace Walpole, who used the term in reference to a fantastic Persian fairy tale- the Three Princes of Serendip. He explained that the princes were capable of discovering items- by accident and sagacity, uncovering items they were not originally seeking.
Since then, the term was used to explain the discovery of penicillin (Alexander Fleming), microwave ovens (Percy Spencer), even CorningWare (Donald Stookey). But, this new finding, this discovery was found by UVA scientists who were looking for something else. (The discovery has been confirmed by a second set of scientists, finding it in humans.)
For decades, we believed that the brain cleared out molecular debris (junk, expended molecules) via a special ecosystem. One we never did quite find. Because the normal system found in the body- the lymphatic system- was really never uncovered in the brain region.
The lymph system is part of the circulatory system (I bet you thought that was just blood vessels and the heart); it carries a clearish liquid, transporting immune cells (that fight infection) and cellular debris (away from the tissues of the body).
Dr. Jonathan Kipnis (senior author), along with Drs. A Louveau (the post doc who actually identified the lymphatic system in mice brains), I Smirnov, TJ Keyes, JD Eccles, SJ Rouhani, JD Peske, NC Derecki, D Castle, JW Mandell, KS Lee, and TH Harris (all of Virginia, in various medical and allied health departments) published “Structural and functional features of central nervous system lymphatic vessels” just recently in Nature. The lymphatic vessels were found in locations near the sinuses and within the three layers of the meninges. This made detection difficult until this discovery, mostly due to the fantastic improvements over the past decade in microscopy.
From the University of Virginia The new map of the lymphatic system
Louveau, the postdoc who first saw these vessels, managed to mount the mouse’s meninges (membranes that cover the brain) on a single microscopic slide. Once he recognized what these structures might be, he began testing to discern if these were indeed lymph vessels. And, once confirmed, the discovery meant the brain is connected to the peripheral immune system (through meningeal lymphatic vessels.
This finding is going to change how we consider autism, multiple sclerosis, Alzheimer’s, and chronic fatigue system, among many other maladies. After all, the lymphatic system normally brings immune cells to the sites of infection- but occasionally the system overreacts and these immune cells then attack the body’s healthy tissues (this is what happens with Rheumatoid arthritis, lupus, multiple sclerosis, and Sjoegren’s). It’s also possible that autism is related to overactive immune responses, as is true for gut microbe ecology. Maybe the amyloid plaques in Alzheimer’s arise because the lymph system is not up to snuff.
As I said above, this finding has since been confirmed in humans. Drs. A Aspelund, S Autila, K Alitalo (all of the University of Helsinki), ST Proulx, S Karaman, M Detmar (Swiss Institute of Technology), and TV Karlsen, and H Wiig (University of Bergen) presented their findings, “A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules” in the Journal of Experimental Medicine; this publication confirms the presence of the lymph system in the brain. Their research did not start with mice, but with the human eye, and they found the lymph system draining from the dura (the outer covering of the brain), the meninges, and within the skull- emptying into the jugular vein.
These are exciting times!
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