Tuesday, July 14, 2015

Amazing Medical Discoveries: The “Missing Link”

Medical research produces new and amazing discoveries on an almost daily basis.  These discoveries take place in any number of areas of research, but they occur at the cellular and molecular levels.  For example, a new protein is discovered or the role of a previously discovered protein is elucidated or a disease is found to be linked to a genetic element. Very rarely does an anatomical discovery make the news. But in a recent paper in Nature a link between the lymphatic system and the brain was reported by researchers from Jonathan Kipnis' lab at the University of Virginia.  The complete separation of the lymphatic system and the brain has been anatomical dogma for quite some time.

Besides draining excess fluid from tissue, lymphatic vessels carry immune cells throughout the body. For decades, researchers had assumed that the lymphatic system stopped short of the brain.  The blood brain barrier (BBB), which prevents the exposure of the brain to many compounds, (toxins, drugs, bacteria etc.)  and separates it from the normal immune system, has always believed to provide "immune privilege" to the brain, exempting it from normal immune surveillance.  While limiting the body’s ability to clear pathogens, immune privilege was thought to avoid inflammatory swelling of the brain within the rigid skull.   

Old and New Representations of the Lymphatic System
Old and New Representations of the Lymphatic System. Credit: University of Virginia Health System.

The discovery originated when Dr. Antoine Louveau, a researcher in Kipnis' lab, mounted the membranes, known as meninges, that cover mouse brains on a slide. In the dural sinuses, which drain blood from the brain, he noticed linear patterns in the arrangement of immune T-cells indicating lymphatic vessels. The trick to observing the vessels was to apply fixative to the brain meninges within the skullcap prior to dissection rather than afterward as one would normally do. Subsequently the vessels have been observed in live animals confirming their function.

These findings begin to explain some poorly understood links between disorders such as autism and gastrointestinal problems in children or neurological diseases like multiple sclerosis and Alzheimer's being linked to changes in immune system function, and autoimmune diseases of the gut, such as Crohn’s disease correlating with psychiatric illness.

The reason I found this discovery intriguing is because I have a number of friends that have been diagnosed with multiple sclerosis (MS).  MS is known to be an example of the immune system attacking the brain, although the reasons are poorly understood. The discovery that lymphatic vessels link the brain to the immune system could transform our understanding of how these attacks occur, and what could stop them.

With all the advances that have been made over the years in biomedical science one almost wonders what is left to discover at the macroscopic level regarding human anatomy.  To have a discovery such as this makes you realize that there is still a great deal that we don't understand about the human body.  It’s not every day when these types of discoveries are made and dogma needs to be rewritten.  To quote Kevin Lee, PhD chairman of the UVA Department of Neuroscience, "They'll have to change the textbooks". 

References:  Louveau A, Smirnov I, Keyes TJ,  Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D4Mandell JW, Lee KS, Harris TH, Kipnis J. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015.

By: BioTek Instruments, Paul Held, PhD., Laboratory Manager

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