Second Study Shows Lymphatic System in The Brain

Discussion in 'Other Research' started by Hello!, Jun 17, 2015.

  1. Hello!

    Hello! Well-Known Member

    The Journal of Experimental Medicine just published this! Note the submission and publication dates at the end.

    http://jem.rupress.org/content/early/2015/06/09/jem.20142290.short

    A Dural Lymphatic Vascular System that Drains Brain Interstitial Fluid and Macromolecules

    Aleksanteri Aspelund,1,2 Salli Antila,1,2 Steven T. Proulx,3 Tine Veronica Karlsen,4 Sinem Karaman,3 Michael Detmar,3 Helge Wiig,4 and Kari Alitalo1,2

    ABSTRACT

    The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.

    Submitted: 8 December 2014
    Accepted: 4 June 2015
     
    Merry likes this.
  2. Hello!

    Hello! Well-Known Member

    Here's a write up from the University of Helsinki:

    http://www.med.helsinki.fi/english/news/2015/20150615_aivoimut.html

    Unraveling the link between brain and lymphatic system
    Researchers at the University of Helsinki and Wihuri Research Institute report an exceptionally surprising finding that argues against all previous anatomy and histology textbook knowledge – lymphatic vessels exist in the central nervous system.

    [​IMG]The authors’ original image shows two dura mater lymphatic vessels (red) running along meningeal blood vessels (green).

    Researcher Aleksanteri Aspelund and colleagues discovered a lymphatic vessel network in the mouse meningeal linings and that these vessels have a direct connection to the body’s systemic lymphatic network.

    Lymphatic circulation forms a network that covers almost the whole body and is especially important to the tissue clearance of excess fluid and macromolecules as well as to the immune defense mechanisms. Until now, the central nervous system has been considered an immune-privileged organ not connected to the lymphatic system.

    – We have recently discovered that in the eye, which is another immune-privileged organ previously considered to lack lymphatic circulation, there exists a lymphatic-like vessel. This lead us to investigate the lymphatic nature of the brain in more detail, says Aspelund, who has been working in Academy Professor KariAlitalo’s research group.

    – However, we didn’t expect to find such an extensive network directly connected to the brain. This incredible finding completely changes our understanding of the brain anatomy and gives a chance to look at brain diseases from a completely new angle, he continues.

    The researchers have done an excellent job in characterizing the structure and function of these previously unknown vessels. They show that these meningeal lymphatic vessels drain out of the skull via the foramina of the base of the skull alongside arteries, veins and cranial nerves.

    These vessels show all molecular hallmarks of the lymphatic vessels and function as a direct clearance routes for the brain and cerebrospinal fluid macromolecules out of the skull and into the deep cervical lymph nodes.

    How the lymphatic vessels managed to escape notice all this time?

    – This is no wonder, says medical student Salli Antila, who has also been working with the project.

    – Lymphatic vessels are so closely attached to the structures inside the meninges that if you don’t know what you’re looking for, you will probably miss them. Although we had already found the vessels, it took some time to develop good imaging methods to visualize the vessels, especially for the structures at the bottom of the skull.

    The discovery has raised several new questions concerning fundamental brain functions and the mechanisms of brain diseases.

    Researchers find it highly possible that lymphatic clearance of the brain might prove to be extremely important in neuro-immunological diseases as well as in diseases characterized by the pathological accumulation of misfolded proteins or fluid into the brain parenchyma, such as Alzheimer’s disease, which affects tens of millions of people worldwide.

    The findings have been published online by Journal of Experimental Medicine.

    [​IMG]

    (Click to enlarge) A schematic image of the novel lymphatic vessel network in the meningeal linings of the brain, discovered by Aleksanteri Aspelund and collaborators. (A) Previously, lymphatic vessels in the nasal mucosa were known to drain cerebrospinal fluid, but it was thoughts that the lymphatic vessels did not extend into the brain. (B-C) The new findings revealed that the dura mater lymphatic system is important for the drainage of brain interstitial fluid, macromolecules and cerebrospinal fluid.
     
    Cort and Merry like this.
  3. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Wow....isn't that something...They talk about an "extensive network"

    "we didn’t expect to find such an extensive network directly connected to the brain. This incredible finding completely changes our understanding of the brain anatomy and gives a chance to look at brain diseases from a completely new angle"

    Jarred Younger has said this will make the brain much easier to study. He also thinks it may provide an entry way for pathogens.....
     
  4. Hello!

    Hello! Well-Known Member

    It makes sense. It could also provide an efficient location to deposit therapeutic treatment for a variety of diseases.

    This statement "They show that these meningeal lymphatic vessels drain out of the skull via the foramina of the base of the skull alongside arteries, veins and cranial nerves." makes me wonder if variable inflammation, as in the kind one feels in the neck lymph nodes, could be putting pressure on the arteries, veins and cranial nerves and obstructing flow in and out of the brain. Lack of oxygen perfusion, waste disposal, and/or nerve conduction could all result from such an obstruction.
     
  5. Recliner

    Recliner Member

    Wow!
    I don't know about the rest of y'all but this seems to make the most sense out of anything I've heard lately!
     
    Hello! likes this.
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