Cerebral venous blood flow regulates intracerebral pressure and brain clearance via meningeal lymphatic vessels
17 affiliations
- 1Paris Brain Institute, Université Pierre et Marie Curie Paris 06, INSERM UMRS 1127, Sorbonne Université, Paris, France
- 2Institut Pasteur, Université de Paris, CNRS UMR 3571, Paris, France
- 3Université Paris Cité, Department of Neurology, AP-HP, Hôpital Lariboisière, FHU NeuroVasc, Paris, France
- 4Department of Anesthesiology, Yale School of Medicine, New Haven, CT, USA
- 5Department of Neuroradiology, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
- 6Paris Cardiovascular Research Center, Université Paris Cité, INSERM U970, Paris, France
- 7Department of Internal Medicine, Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT, USA
- 8Institut Pasteur, Université de Paris Cité, INSERM U1224, Paris, France
- 9Yale University, New Haven, CT, USA
- 10Department of Neurology, Yale University School of Medicine, New Haven, CT, USA
- 11Laboratoire Hématologie, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France
- 12Optimisation Thérapeutique en Neuropsychopharmacologie, INSERM U1144, Paris, France
- 13Department of Surgery, Beth Israel Deaconess Medical center, Harvard Medical School, Boston, MA, USA
- 14Université Paris Cité, Department of Neurology, AP-HP, Hôpital Lariboisière, FHU NeuroVasc 2030, Institut Universitaire de France, Paris, France
- 15Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA
- 16Department of Neuroradiology, AP-HP, Pitié-Salpêtrière Hospital, Paris, France. [email protected]
- 17Paris Brain Institute, Université Pierre et Marie Curie Paris 06, INSERM UMRS 1127, Sorbonne Université, Paris, France. [email protected]
Abstract
The vascular system regulates brain clearance through arterial blood flow and lymphatic drainage of cerebrospinal fluid (CSF). Idiopathic intracranial hypertension (IIH), characterized by elevated intracranial pressure and dural venous sinus stenoses, can be treated by restoring venous blood flow via venous stenting, suggesting a role for venous blood flow in brain fluid clearance. Using magnetic resonance imaging (MRI) in IIH patients and healthy controls, we identified that dural venous stenoses in IIH were associated with impaired lymphatic drainage, perivenous fluid retention, and brain fluid accumulation. To investigate this further, we developed a mouse model with bilateral jugular vein ligation (JVL), which recapitulated key human findings, including intracranial hypertension, calvarial lymphatic regression, and brain swelling due to impaired clearance. To further dissect the respective roles of dural lymphatics and venous blood flow in brain clearance, we performed JVL in mice with dural lymphatic depletion. These mice exhibited spontaneous elevated intracranial pressure, but JVL did not further exacerbate this effect. Moreover, the synchronous restoration of brain clearance and dural lymphatics observed in mice after JVL was absent in lymphatic-deficient mice.Transcriptomic analyses revealed that lymphatic remodeling induced by JVL was driven by VEGF-C signaling between dural mesenchymal and lymphatic endothelial cells. These findings establish the dural venous sinuses as a critical platform where venous blood flow interacts with mesenchymal cells to preserve dural lymphatic integrity and function, essential for brain fluid clearance.
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BibTeX
@article{kamouh2026cerebral,
title = {{Cerebral venous blood flow regulates intracerebral pressure and brain clearance via meningeal lymphatic vessels}},
author = {Marie-Renée El Kamouh and Myriam Spajer and Ruchith Singhabahu and Anne-Laure Joly Marolany and Kurt A. Sailor and Laura Mouton and Diana Doukhi and Sunil Koundal and Tanner Metcalfe and Dominique Langui and Abel Grine and Kevin Boyé and Felipe Saceanu Leser and Justus Ninnemann and Joshua Gottschalk and Cyrus Sadeghi and Xu Han and Lígia Simões Braga Boisserand and David Akbar and Jérôme Van Wassenhove and Anthony Ruze and Amelle Nasry and Marie‐Charlotte Bourrienne and Elora Buscher and Young‐Kwon Hong and Mikaël Mazighi and Pierre‐Marie Lledo and Helene Benveniste and Mathieu David Santin and Anne Eichmann and Stéphane Lehéricy and Jean‐Léon Thomas and Stéphanie Lenck},
journal = {Nature Neuroscience},
year = {2026},
month = jul,
doi = {10.1038/s41593-026-02358-1},
url = {https://doi.org/10.1038/s41593-026-02358-1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Cerebral venous blood flow regulates intracerebral pressure and brain clearance via meningeal lymphatic vessels
AU - Marie-Renée El Kamouh
AU - Myriam Spajer
AU - Ruchith Singhabahu
AU - Anne-Laure Joly Marolany
AU - Kurt A. Sailor
AU - Laura Mouton
AU - Diana Doukhi
AU - Sunil Koundal
AU - Tanner Metcalfe
AU - Dominique Langui
AU - Abel Grine
AU - Kevin Boyé
AU - Felipe Saceanu Leser
AU - Justus Ninnemann
AU - Joshua Gottschalk
AU - Cyrus Sadeghi
AU - Xu Han
AU - Lígia Simões Braga Boisserand
AU - David Akbar
AU - Jérôme Van Wassenhove
AU - Anthony Ruze
AU - Amelle Nasry
AU - Marie‐Charlotte Bourrienne
AU - Elora Buscher
AU - Young‐Kwon Hong
AU - Mikaël Mazighi
AU - Pierre‐Marie Lledo
AU - Helene Benveniste
AU - Mathieu David Santin
AU - Anne Eichmann
AU - Stéphane Lehéricy
AU - Jean‐Léon Thomas
AU - Stéphanie Lenck
PY - 2026
DA - 2026/07/22
JO - Nature Neuroscience
DO - 10.1038/s41593-026-02358-1
UR - https://doi.org/10.1038/s41593-026-02358-1
AB - The vascular system regulates brain clearance through arterial blood flow and lymphatic drainage of cerebrospinal fluid (CSF). Idiopathic intracranial hypertension (IIH), characterized by elevated intracranial pressure and dural venous sinus stenoses, can be treated by restoring venous blood flow via venous stenting, suggesting a role for venous blood flow in brain fluid clearance. Using magnetic resonance imaging (MRI) in IIH patients and healthy controls, we identified that dural venous stenoses in IIH were associated with impaired lymphatic drainage, perivenous fluid retention, and brain fluid accumulation. To investigate this further, we developed a mouse model with bilateral jugular vein ligation (JVL), which recapitulated key human findings, including intracranial hypertension, calvarial lymphatic regression, and brain swelling due to impaired clearance. To further dissect the respective roles of dural lymphatics and venous blood flow in brain clearance, we performed JVL in mice with dural lymphatic depletion. These mice exhibited spontaneous elevated intracranial pressure, but JVL did not further exacerbate this effect. Moreover, the synchronous restoration of brain clearance and dural lymphatics observed in mice after JVL was absent in lymphatic-deficient mice.Transcriptomic analyses revealed that lymphatic remodeling induced by JVL was driven by VEGF-C signaling between dural mesenchymal and lymphatic endothelial cells. These findings establish the dural venous sinuses as a critical platform where venous blood flow interacts with mesenchymal cells to preserve dural lymphatic integrity and function, essential for brain fluid clearance.
SN - 1097-6256
SN - 1546-1726
ER -