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The Brain's Immune System

THE XTALKS BLOG

June 23, 2015 | by Michelle Muller

The Brain's Immune System

It is hard to imagine there is a system in the body that has not yet been mapped, but a breakthrough study published in Nature this month has identified structural and functional features of the brain’s previously unknown lymphatic system.

The lymphatic system is an important component of the immune and circulatory system, recycling interstitial fluid and waste products from cells. Lymphatic vessels carry fluid and immune cells from tissues to lymph nodes in the body, and are lined by endothelial cells, smooth muscle, and connective tissue. Mechanisms of the brain’s clearance mechanisms have remained poorly understood, but as this research reveals, the brain appears connected to the peripheral immune system through meningeal lymphatic vessels.

The meninges comprises three different layers surrounding the brain: dura mater, being the outermost and closest to the skull, the pia, mater closest to the brain, and the arachnoid mater, in between, containing spongy connective tissue and cerebrospinal fluid (CSF) in a subarachnoid space.


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The researchers were looking for potential routes of surveying immune cells and investigated the meningeal spaces in the brains of mice. Using a technique to fix the meninges within the skull cap in order to examine its physiological condition, the researchers could stain for markers of immune and endothelial cells. They noticed specific abluminal patterns of staining near dural sinuses, where blood vessels drain into the internal jugular veins. It was found these vessels did not belong to cardiovasculature, but stained positively for lymphatic markers similar to peripheral lymphatic vessels.

However, there are two types of lymphatic vessels – initial and collecting, which differ in vessel structure, adhesion molecules, and permeability. The lymphatic vessels in the meninges display characteristic features of the initial type, devoid of smooth muscle cells and have patterns of adhesion molecules similar to diaphragm lymphatic vessels. Other unique attributes include the organization of the network, starting from both eyes and aligning adjacent to the sinuses, composed of narrower vessels and less complex than other tissues. The researchers proved the functionality of the meningeal lymphatic vessels to carry fluid and cells from the CSF by injecting fluorescent tracers and dyes to track their drainage into the deep cervical lymph nodes.

This study complements another breakthrough study in 2012 that discovered a ‘glymphatic system’ in the brain, a pathway of clearance for interstitial fluid through long projections of astrocytes (glial cells) containing aquaporin channels. These peri-vascular projections called ‘end-feet’ form an envelope around brain vasculature and allow bulk interstitial flow and CSF exchange, including solutes such as clearance of Amyloid-beta peptides. This was the first major finding of lymphatic cleansing of brain interstitial fluid, and these new findings may be the secondary step involved in draining of interstitial fluid from the brain into the periphery.

These findings have major implications for many neurodegenerative diseases associated with immune system dysfunction, including Alzheimer’s, Huntington’s, Parkinson’s, Multiple Sclerosis, ALS, and many more brain diseases related to immune activation.

Source: Nature Letter, June 1 2015 “Structural and functional features of central nervous system lymphatic vessels”

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Keywords: The Brain, Immune Cells


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