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Neuroscientists – myself included – like to think the brain reigns supreme, the organ to rule all other organ systems. It asserts complete control over respiratory and cardiovascular systems, demanding air and blood to carry out its sophisticated operations. It even has a moat in the form of a blood-brain barrier, making it “immune privileged,” with an esoteric immune system that we don’t quite understand. It is untouchable. At least it was, until now…
In an affront to years of textbook knowledge that the brain is separate from the body’s immune system, a recent study suggests that the brain and immune system are in fact quite intertwined (Louveau et al., 2015). With the use of numerous types of antibodies, the authors found that the passages for immune cells, known as lymphatic vessels, were closely intertwined with brain blood vessels.
How have we missed these lymphatic vessels this whole time? As the authors write: “The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system.” In short, the vessels were found in the protective covering of the brain, known as the meninges, which most researchers simply remove and discard. To address this problem, the University of Virginia researchers developed a whole-mount dissection of the meninges, allowing them to locate all of the major sinuses and look for signs of the immune system.
After staining the meninges for T cells and lymphatic endothelial cells, they saw that there were many T cells aligned with the major blood vessels. They continued to look for different markers, including Lyve-1, which marks lymphatic endothelial cells. Like the T cells, they found that Lyve-1 was present in cells along the sinuses. All told, the process was a remarkable tour de force using 14 different antibodies to locate immune system markers. While this work was done in mice, they went on to find similar Lyve-1+ structures in human dura (the thickest part of the meninges), but were not able to fully characterize it given a limited amount of tissue. As mice are indeed different to humans, critics see this as a serious limitation of the study.
However, In mice at least, the researchers found several unique characteristics of these vessels, noting that they were narrower and formed a less complex network than in the peripheral immune system. While it’s unclear what this might mean for how these vessels function, they speculated that the high pressure from cerebrospinal fluid in the brain may limit the branching of the vessels.
Finally, in order to test the function of these lymphatic vessels, the researchers injected fluorescent tracers into the ventricles of the brain, to see if they would enter the nearby vessels. Indeed, the vessels in the brain appear to be connected functionally, facilitating the passage of cerebrospinal fluid from brain blood vessels to the lymph nodes. Although this is a more “traditional” path for the drainage of fluid from blood vessels, it is the first time it has been observed in the central nervous system.
All the hype surrounding this finding is not just about its novelty – it is also about the clinical implications. Autoimmune diseases often occur in parallel with neurological symptoms, and these structures might be to blame. If the brain cannot drain fluid properly, it may begin to malfunction in other ways that affect our behavior. In diseases like multiple sclerosis (MS), failure in the brain’s immune system might be directly linked to myelin loss and the corresponding cognitive and motor deficits. Importantly, however, these observations are in the covering of the brain, not in the brain itself, which means drawing conclusions about the relation between the immune system and brain remains a little tricky. As always, more research will need to be done to elucidate the function of these vessels and their potential role in autoimmune disorders.
As neurotechnologies has advanced over the past decade, there has been marked by an insurgence of labs and departments moving towards brain science. This study demonstrates the power of this approach: by integrating expertise from other fields such as immunology into our understanding of the brain, we can begin to place it in the context of the body, rather than on it’s own separate pedestal. We’re connected, from head to toe, whether stubborn neuroscientists like myself like to admit it or not.
Ashley Juavinett is a UCSD neurosciences PhD student, an NSF Graduate Research Fellow, and an aspiring science writer. Working at the Salk Institute (La Jolla, CA), Ashley is using in vivo imaging to investigate the neural circuitry underlying visual perception in mice. She currently co-directs a collaborative science writing group, NeuWrite San Diego (http://www.neuwriteSD.org), and writes about neuroscience and society on her own blog (http://scramblingforsignificance.blogspot.com). Follow her on Twitter: @ashleyjthinks