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Cited by 264Cerebrospinal fluid and hydrocephalusBarrier Structure and Function StudiesNeurosurgical Procedures and Complications

Identification of direct connections between the dura and the brain

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Smyth, Leon C. D., Xu, Di, Okar, Serhat V., Dykstra, Taitea, Rustenhoven, Justin, Papadopoulos, Zachary, Bhasiin, Kesshni, Kim, Min Woo +14 more·2024·Nature
DOI 10.1038/s41586-023-06993-7PMC PMC11254388
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Abstract

The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between the central nervous system and the dura mater is crucial for waste clearance and immune surveillance 1,2. How the arachnoid barrier balances separation and communication is poorly understood. Here, using transcriptomic data, we developed transgenic mice to examine specific anatomical structures that function as routes across the arachnoid barrier. Bridging veins create discontinuities where they cross the arachnoid barrier, forming structures that we termed arachnoid cuff exit (ACE) points. The openings that ACE points create allow the exchange of fluids and molecules between the subarachnoid space and the dura, enabling the drainage of cerebrospinal fluid and limited entry of molecules from the dura to the subarachnoid space. In healthy human volunteers, magnetic resonance imaging tracers transit along bridging veins in a similar manner to access the subarachnoid space. Notably, in neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, ACE points also enable cellular trafficking, representing a route for immune cells to directly enter the subarachnoid space from the dura mater. Collectively, our results indicate that ACE points are a critical part of the anatomy of neuroimmune communication in both mice and humans that link the central nervous system with the dura and its immunological diversity and waste clearance systems.

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Authors
Smyth, L. C. D., Xu, D., Okar, S. V., Dykstra, T., Rustenhoven, J., Papadopoulos, Z., Bhasiin, K., Kim, M. W., Drieu, A., Mamuladze, T., Blackburn, S., Gu, X., Gaitán, M. I., Nair, G., Storck, S. E., Du, S., White, M. A., Bayguinov, P., Smirnov, I., Dikranian, K., Reich, D. S., & Kipnis, J.
Affiliations
  • Washington University in St. Louis (US)
  • National Institutes of Health (US)
  • University of Auckland (NZ)
Corresponding author
  • Smyth, Leon C. D.
  • Kipnis, Jonathan
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2024-02-07
Volume
627
Issue
8002
Pages
165-173
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-023-06993-7
PMC
PMC11254388
OpenAlex
W4391617027
Cited by
264
References
17
Citations by year
2026: 107 · 2025: 96 · 2024: 61
FWCI
46.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Washington University in St. Louis
  • Cure Alzheimer's Fund
  • National Institutes of Health (AG034113)
  • Center for Cellular Imaging, Washington University
  • National Institute on Aging (R01AG034113, R37AG034113, P01AG078106)
  • National Institute of Mental Health
  • National Institute of General Medical Sciences (T32GM007200)
  • National Institute of Neurological Disorders and Stroke (ZIANS003119)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Neurology › Neurosurgical Procedures and Complications
Keywords
dura mater, bridging veins, cerebrospinal fluid drainage, subarachnoid space, neuroimmune interactions, immune cell trafficking, experimental autoimmune encephalomyelitis, waste clearance, transgenic mice
MeSH terms
Animals, Arachnoid, Biological Transport, Brain, Cerebrospinal Fluid, Dura Mater, Encephalomyelitis, Autoimmune, Experimental, Humans, Magnetic Resonance Imaging, Meninges, Mice, Transgenic, Subarachnoid Space, Veins, Gene Expression Profiling, Mice

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