Anatomy and function of the vertebral column lymphatic network in mice

Jacob, Laurent; Boisserand, Lígia Simões Braga; Geraldo, Luiz Henrique Medeiros; Neto, Jose de Brito; Mathivet, Thomas; Antila, Salli; Barka, Besma; Xu, Yunling; Thomas, Jean-Mickael; Pestel, Juliette; Aigrot, Marie‐Stéphane; Song, Eric; Nurmi, Harri; Lee, Seyoung; Alitalo, Kari; Renier, Nicolas; Eichmann, Anne; Thomas, Jean‐Léon

doi:10.1038/s41467-019-12568-w

Cited by 104 publications

(110 citation statements)

References 59 publications

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“…It has been proposed that at this particular site the arachnoid barrier is lacking, providing potential access to lymphatic vessels located within the spinal dura mater or in epidural tissue (Zenker et al, 1994). While these networks of lymphatic vessels have been found to be particularly enriched at the cervical and thoracic regions (Antila et al, 2017; Jacob et al, 2019 Preprint ; Miura et al, 1998), we could detect CSF outflow predominantly at the caudal end. Both postmortem near-infrared fluorescence imaging in Prox1-GFP mice and in vivo MRI indicated a lack of significant outflow at other spinal locations.…”

Section: Resultsmentioning

confidence: 51%

Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Decker

Müller

et al. 2019

Journal of Experimental Medicine

101

106

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The pathways of circulation and clearance of cerebrospinal fluid (CSF) in the spine have yet to be elucidated. We have recently shown with dynamic in vivo imaging that routes of outflow of CSF in mice occur along cranial nerves to extracranial lymphatic vessels. Here, we use near-infrared and magnetic resonance imaging to demonstrate the flow of CSF tracers within the spinal column and reveal the major spinal pathways for outflow to lymphatic vessels in mice. We found that after intraventricular injection, a spread of CSF tracers occurs within both the central canal and the spinal subarachnoid space toward the caudal end of the spine. Outflow of CSF tracers from the spinal subarachnoid space occurred predominantly from intravertebral regions of the sacral spine to lymphatic vessels, leading to sacral and iliac LNs. Clearance of CSF from the spine to lymphatic vessels may have significance for many conditions, including multiple sclerosis and spinal cord injury.

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Section: Resultsmentioning

confidence: 51%

Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Decker

Müller

et al. 2019

Journal of Experimental Medicine

101

106

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“…The dural sac can move in the longitudinal direction of 2-4 mm, a measure which coincides with the movement of the nervous system [47]. The spinal lymphatic system is found in the epidural space, together with adipose tissue [48]. The pial spinal layer has a great capacity to withstand longitudinal mechanical stresses and their distributions, despite its small thickness (from 0.089 to 1.40 MPa) [49][50].…”

Section: The Mobility Of the Cranial And Spinal Meningeal Membranesmentioning

confidence: 96%

The Cranial Bowl in the New Millennium and Sutherland's Legacy for Osteopathic Medicine: Part 1

Bordoni

Walkowski²,

Ducoux³

et al. 2020

Cureus

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A theoretical model that does not evolve with new information deriving from scientific research, by changing the assumptions from which it was born, becomes a philosophy; the scientist becomes a scholarch. Cranial manual osteopathic medicine is very controversial, although it is commonly practiced, from the clinician to the nonmedical health worker. The article, divided into two parts, reviews the assumptions with which the cranial model was created, highlighting the scientific innovations and new anatomical-physiological reflections. In the first part we will review the synthesis and movement of cerebrospinal fluid (CSF), the movement of the central and peripheral nervous system; we will highlight the mechanical characteristics of the meninges. The aim of the article is to highlight the need to renew the existing cranial model.

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“…Complementary approches have detected both extracranial 6,7,13 and intracranial 9,10,11,12 lymphatic exits of CSF-injected tracers and suggest that the CSF is absorbed by two lymphatic pathways, one external and the other one internal to the skull and vertebral column. The main part of CSF drainage rapidly occurs through lymphatic vessels located rostrally, outside of the skull in the nasal mucosa, through channels of the cribriform plate of the ethmoid bone 3,6,13 and, caudally, outside of lumbosacral vertebral bones through dorsolateral routes that are not yet fully characterized 7,14 . In addition, in the meninges of the skull, lymphatic capillaries of the dura mater directy absorb CSF and meningeal immune cells toward dural lymphatic collectors that cross the skull bones and connect to CNS-draining LNs 12,14 .…”

Section: Introductionmentioning

confidence: 99%

“…The main part of CSF drainage rapidly occurs through lymphatic vessels located rostrally, outside of the skull in the nasal mucosa, through channels of the cribriform plate of the ethmoid bone 3,6,13 and, caudally, outside of lumbosacral vertebral bones through dorsolateral routes that are not yet fully characterized 7,14 . In addition, in the meninges of the skull, lymphatic capillaries of the dura mater directy absorb CSF and meningeal immune cells toward dural lymphatic collectors that cross the skull bones and connect to CNS-draining LNs 12,14 . These meningeal lymphatic vessels play important roles in CNS pathophysiology, because brain meningeal lymphatics are altered upon aging and also impact the outcome of neurological brain diseases, .…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Imaging of the Vertebral Lymphatic Vasculature and Drainage using iDISCO<sup>+</sup> and Light Sheet Fluorescence Microscopy

Jacob

Brito

Thomas

2020

JoVE

Self Cite

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The lymphatic system associated with the central nervous system (CNS) includes the lymphatic vasculature that spins around the brain, the spinal cord, and its associated LNs. The CNS-associated lymphatic system is involved in the drainage of CSF macromolecules and meningeal immune cells toward CNS-draining LNs, thereby regulating waste clearance and immune surveillance within CNS tissues. Presented is a novel approach to obtain three-dimensional (3D) and cellular resolution images of CNS-associated lymphatics while preserving the integrity of their circuits within surrounding tissues. The iDISCO + protocol is used to immunolabel lymphatic vessels in decalcified and cleared whole mount preparations of the vertebral column that are subsequently imaged with light sheet fluorescence microscopy (LSFM). The technique reveals the 3D structure of the lymphatic network connecting the meningeal and epidural spaces around the spinal cord to extravertebral lymphatic vessels. Provided are 3D images of the drainage circuits of molecular tracers previously injected into either the CSF via the cisterna magna or the thoracolumbar spinal parenchyma. The iDISCO + /LSFM approach brings unprecedented opportunities to explore the structure and function of the CNS-associated lymphatic system in neurovascular biology, neuroimmunology, brain and vertebral cancer, or vertebral bone and joint biology.

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Anatomy and function of the vertebral column lymphatic network in mice

Cited by 104 publications

References 59 publications

Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

The Cranial Bowl in the New Millennium and Sutherland's Legacy for Osteopathic Medicine: Part 1

Three-Dimensional Imaging of the Vertebral Lymphatic Vasculature and Drainage using iDISCO<sup>+</sup> and Light Sheet Fluorescence Microscopy

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