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Implications profound for neurological diseases from autism to Alzheimer\u2019s to multiple sclerosis.<\/strong><\/p>\n

In a stunning discovery that overturns decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer\u2019s disease to multiple sclerosis.<\/p>\n

\u201cInstead of asking, \u2018How do we study the immune response of the brain?\u2019 \u2018Why do multiple sclerosis patients have the immune attacks?\u2019 now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels,\u201d said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA\u2019s Center for Brain Immunology and Glia (BIG). \u201cIt changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can\u2019t be studied. But now we can ask mechanistic questions.\u201d<\/p>\n

\u201cWe believe that for every neurological disease that has an immune component to it, these vessels may play a major role,\u201d Kipnis said. \u201cHard to imagine that these vessels would not be involved in a [neurological] disease with an immune component.\u201d<\/p>\n

New Discovery in Human Body<\/strong><\/p>\n

Kevin Lee, PhD, chairman of the UVA Department of Neuroscience, described his reaction to the discovery by Kipnis\u2019 lab: \u201cThe first time these guys showed me the basic result, I just said one sentence: \u2018They\u2019ll have to change the textbooks.\u2019 There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation \u2013 and they\u2019ve done many studies since then to bolster the finding \u2013 that it will fundamentally change the way people look at the central nervous system\u2019s relationship with the immune system.\u201d<\/p>\n

Even Kipnis was skeptical initially. \u201cI really did not believe there are structures in the body that we are not aware of. I thought the body was mapped,\u201d he said. \u201cI thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not.\u201d<\/p>\n

\u2018Very Well Hidden\u2019<\/strong><\/p>\n

The discovery was made possible by the work of Antoine Louveau, PhD, a postdoctoral fellow in Kipnis\u2019 lab. The vessels were detected after Louveau developed a method to mount a mouse\u2019s meninges \u2013 the membranes covering the brain \u2013 on a single slide so that they could be examined as a whole. \u201cIt was fairly easy, actually,\u201d he said. \u201cThere 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\u2019t have worked.\u201d<\/p>\n

After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and there they were. The impossible existed. The soft-spoken Louveau recalled the moment: \u201cI called Jony [Kipnis] to the microscope and I said, \u2018I think we have something.’\u201d<\/p>\n

\"This<\/a><\/p>\n

Maps of the lymphatic system: old (left) and updated to reflect UVA\u2019s discovery. Image credit: University of Virginia Health System.<\/p>\n

As to how the brain\u2019s lymphatic vessels managed to escape notice all this time, Kipnis described them as \u201cvery well hidden\u201d and noted that they follow a major blood vessel down into the sinuses, an area difficult to image. \u201cIt\u2019s so close to the blood vessel, you just miss it,\u201d he said. \u201cIf you don\u2019t know what you\u2019re after, you just miss it.\u201d<\/p>\n

\u201cLive imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris,\u201d Kipnis noted. Harris, a PhD, is an assistant professor of neuroscience and a member of the BIG center. Kipnis also saluted the \u201cphenomenal\u201d surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.<\/p>\n

Alzheimer\u2019s, Autism, MS and Beyond<\/strong><\/p>\n

The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it. For example, take Alzheimer\u2019s disease. \u201cIn Alzheimer\u2019s, there are accumulations of big protein chunks in the brain,\u201d Kipnis said. \u201cWe think they may be accumulating in the brain because they\u2019re not being efficiently removed by these vessels.\u201d He noted that the vessels look different with age, so the role they play in aging is another avenue to explore. And there\u2019s an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.<\/p>\n

About this neuroscience research<\/div>\n

The findings have been published online by the prestigious journal Nature<\/em> and will appear in a forthcoming print edition. The article was authored by Louveau, Smirnov, Timothy J. Keyes, Jacob D. Eccles, Sherin J. Rouhani, J. David Peske, Noel C. Derecki, David Castle, James W. Mandell, Lee, Harris and Kipnis.<\/p>\n

Funding:<\/strong> The study was funded by National Institutes of Health grants R01AG034113 and R01NS061973. Louveau was a fellow of Fondation pour la Recherche Medicale.<\/p>\n

Source:<\/strong> Debra Kain \u2013 University of Virginia Health System<\/a>
\nImage Source:<\/strong> The image is credited to the University of Virginia Health System
\nOriginal Research:<\/strong> Abstract<\/a> for \u201cStructural and functional features of central nervous system lymphatic vessels\u201d by Antoine Louveau, Igor Smirnov, Timothy J. Keyes, Jacob D. Eccles, Sherin J. Rouhani, J. David Peske, Noel C. Derecki, David Castle, James W. Mandell, Kevin S. Lee, Tajie H. Harris and Jonathan Kipnis in Nature<\/em>. Published online June 1 2015 doi:10.1038\/nature14432<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Implications profound for neurological diseases from autism to Alzheimer\u2019s to multiple sclerosis. In a stunning discovery that overturns decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to…<\/span><\/p>\n

Read more ›<\/a><\/div>\n

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