Understanding the functions and relationships of the glymphatic system and meningeal lymphatics
Antoine Louveau,1 Benjamin A. Plog,2 Salli Antila,3 Kari Alitalo,3 Maiken Nedergaard,2,4 and Jonathan Kipnis1
1Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
2Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA.
3Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
4Center of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Address correspondence to Kari Alitalo, Wihuri Research Institute and Molecular Cancer Biology Program, Biomedicum Helsinki, 00014 University of Helsink, Haartmaninkatu 8, Helsinki, Finland. Phone: 358.9.191.25511; Email: kari.alitalo@helsinki.fi. Or to: Maiken Nedergaard, Center of Translational Neuromedicine, University of Rochester Medical School, 609 Elmwood Avenue, Rochester, New York 14642, USA. Phone: 585.478.0610; Email: Maiken_Nedergaard@URMC.Rochester.edu. Or to: Jonathan Kipnis, 409 Lane Rd, MR4 Building, Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908, USA. Phone: 434.983.3858; Email: kipnis@virginia.edu.
Authorship note: A. Louveau, B.A. Plog, and S. Antila contributed equally to this work. K. Alitalo, M. Nedergaard, and J. Kipnis contributed equally to this work and are co–senior authors.
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1Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
2Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA.
3Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
4Center of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Address correspondence to Kari Alitalo, Wihuri Research Institute and Molecular Cancer Biology Program, Biomedicum Helsinki, 00014 University of Helsink, Haartmaninkatu 8, Helsinki, Finland. Phone: 358.9.191.25511; Email: kari.alitalo@helsinki.fi. Or to: Maiken Nedergaard, Center of Translational Neuromedicine, University of Rochester Medical School, 609 Elmwood Avenue, Rochester, New York 14642, USA. Phone: 585.478.0610; Email: Maiken_Nedergaard@URMC.Rochester.edu. Or to: Jonathan Kipnis, 409 Lane Rd, MR4 Building, Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908, USA. Phone: 434.983.3858; Email: kipnis@virginia.edu.
Authorship note: A. Louveau, B.A. Plog, and S. Antila contributed equally to this work. K. Alitalo, M. Nedergaard, and J. Kipnis contributed equally to this work and are co–senior authors.
Find articles by Plog, B. in: JCI | PubMed | Google Scholar
1Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
2Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA.
3Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
4Center of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Address correspondence to Kari Alitalo, Wihuri Research Institute and Molecular Cancer Biology Program, Biomedicum Helsinki, 00014 University of Helsink, Haartmaninkatu 8, Helsinki, Finland. Phone: 358.9.191.25511; Email: kari.alitalo@helsinki.fi. Or to: Maiken Nedergaard, Center of Translational Neuromedicine, University of Rochester Medical School, 609 Elmwood Avenue, Rochester, New York 14642, USA. Phone: 585.478.0610; Email: Maiken_Nedergaard@URMC.Rochester.edu. Or to: Jonathan Kipnis, 409 Lane Rd, MR4 Building, Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908, USA. Phone: 434.983.3858; Email: kipnis@virginia.edu.
Authorship note: A. Louveau, B.A. Plog, and S. Antila contributed equally to this work. K. Alitalo, M. Nedergaard, and J. Kipnis contributed equally to this work and are co–senior authors.
Find articles by Antila, S. in: JCI | PubMed | Google Scholar
1Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
2Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA.
3Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
4Center of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Address correspondence to Kari Alitalo, Wihuri Research Institute and Molecular Cancer Biology Program, Biomedicum Helsinki, 00014 University of Helsink, Haartmaninkatu 8, Helsinki, Finland. Phone: 358.9.191.25511; Email: kari.alitalo@helsinki.fi. Or to: Maiken Nedergaard, Center of Translational Neuromedicine, University of Rochester Medical School, 609 Elmwood Avenue, Rochester, New York 14642, USA. Phone: 585.478.0610; Email: Maiken_Nedergaard@URMC.Rochester.edu. Or to: Jonathan Kipnis, 409 Lane Rd, MR4 Building, Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908, USA. Phone: 434.983.3858; Email: kipnis@virginia.edu.
Authorship note: A. Louveau, B.A. Plog, and S. Antila contributed equally to this work. K. Alitalo, M. Nedergaard, and J. Kipnis contributed equally to this work and are co–senior authors.
Find articles by Alitalo, K. in: JCI | PubMed | Google Scholar
1Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
2Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA.
3Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
4Center of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Address correspondence to Kari Alitalo, Wihuri Research Institute and Molecular Cancer Biology Program, Biomedicum Helsinki, 00014 University of Helsink, Haartmaninkatu 8, Helsinki, Finland. Phone: 358.9.191.25511; Email: kari.alitalo@helsinki.fi. Or to: Maiken Nedergaard, Center of Translational Neuromedicine, University of Rochester Medical School, 609 Elmwood Avenue, Rochester, New York 14642, USA. Phone: 585.478.0610; Email: Maiken_Nedergaard@URMC.Rochester.edu. Or to: Jonathan Kipnis, 409 Lane Rd, MR4 Building, Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908, USA. Phone: 434.983.3858; Email: kipnis@virginia.edu.
Authorship note: A. Louveau, B.A. Plog, and S. Antila contributed equally to this work. K. Alitalo, M. Nedergaard, and J. Kipnis contributed equally to this work and are co–senior authors.
Find articles by Nedergaard, M. in: JCI | PubMed | Google Scholar
1Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
2Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA.
3Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
4Center of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Address correspondence to Kari Alitalo, Wihuri Research Institute and Molecular Cancer Biology Program, Biomedicum Helsinki, 00014 University of Helsink, Haartmaninkatu 8, Helsinki, Finland. Phone: 358.9.191.25511; Email: kari.alitalo@helsinki.fi. Or to: Maiken Nedergaard, Center of Translational Neuromedicine, University of Rochester Medical School, 609 Elmwood Avenue, Rochester, New York 14642, USA. Phone: 585.478.0610; Email: Maiken_Nedergaard@URMC.Rochester.edu. Or to: Jonathan Kipnis, 409 Lane Rd, MR4 Building, Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908, USA. Phone: 434.983.3858; Email: kipnis@virginia.edu.
Authorship note: A. Louveau, B.A. Plog, and S. Antila contributed equally to this work. K. Alitalo, M. Nedergaard, and J. Kipnis contributed equally to this work and are co–senior authors.
Find articles by Kipnis, J. in: JCI | PubMed | Google Scholar
First published September 1, 2017 - More info
J Clin Invest. 2017;127(9):3210–3219. doi:10.1172/JCI90603.
Copyright © 2017, American Society for Clinical Investigation
Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems.
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