TY - JOUR
T1 - Understanding the functions and relationships of the glymphatic system and meningeal lymphatics
AU - Louveau, Antoine
AU - Plog, Benjamin A.
AU - Antila, Salli
AU - Alitalo, Kari
AU - Nedergaard, Maiken
AU - Kipnis, Jonathan
N1 - Funding Information:
We thank A. Impagliazzo for the contributions to figure development and S. Smith for editing sections of the manuscript. This work was supported by grants from the NIH (AG034113 and NS096967) and the National Multiple Sclerosis Society to JK; from Jane and Aatos Erkko Foundation, the European Research Coun- cil (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement 743155, the Academy of Finland Centre of Excellence Program 2014-2019 (271845), and the Sigrid Juselius Foundation (all to KA). SA has been supported by Biomedicum Helsinki Foundation, The Finnish Medical Foundation, Orion Research Foundation, and Finnish Cultural Foundation. This work was also supported by the NIH (R01NS100366 and R01AG048769) and the Novo Nordisk Research Foundation to MN, and by the LE&RN Postdoctoral Fellowship Award (to AL).
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85028914493&partnerID=8YFLogxK
U2 - 10.1172/JCI90603
DO - 10.1172/JCI90603
M3 - Review article
C2 - 28862640
AN - SCOPUS:85028914493
SN - 0021-9738
VL - 127
SP - 3210
EP - 3219
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 9
ER -