In vivo assessment of cerebrospinal fluid efflux to nasal mucosa in humans

Melin, Erik; Eide, Per Kristian; Ringstad, Geir

doi:10.1038/s41598-020-72031-5

Cited by 40 publications

(46 citation statements)

References 42 publications

(77 reference statements)

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“…In contrast, in animal models dyes infused into the cisterna magna can flow through the cribriform plate and be found quite distally in the nasal mucosa away from the cribriform plate when viewed sagittally. Interestingly, two recent reports using MRI in humans revealed the lack of CSF efflux through the cribriform plate into the nasal epithelium, despite the accumulation of CSF on the CNS side of the cribriform plate where the meningeal lymphatics reside ( Melin et al, 2020 ; Ringstad and Eide, 2020 ). Of note, these studies were done in patients that had intracranial hypertension, which may explain some of the confounding results between human studies.…”

Section: Comparing Animal Models With Human Studiesmentioning

confidence: 99%

Neuroinflammation-Driven Lymphangiogenesis in CNS Diseases

Hsu

Laaker

Sándor

et al. 2021

Front. Cell. Neurosci.

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The central nervous system (CNS) undergoes immunosurveillance despite the lack of conventional antigen presenting cells and lymphatic vessels in the CNS parenchyma. Additionally, the CNS is bathed in a cerebrospinal fluid (CSF). CSF is continuously produced, and consequently must continuously clear to maintain fluid homeostasis despite the lack of conventional lymphatics. During neuroinflammation, there is often an accumulation of fluid, antigens, and immune cells to affected areas of the brain parenchyma. Failure to effectively drain these factors may result in edema, prolonged immune response, and adverse clinical outcome as observed in conditions including traumatic brain injury, ischemic and hypoxic brain injury, CNS infection, multiple sclerosis (MS), and brain cancer. Consequently, there has been renewed interest surrounding the expansion of lymphatic vessels adjacent to the CNS which are now thought to be central in regulating the drainage of fluid, cells, and waste out of the CNS. These lymphatic vessels, found at the cribriform plate, dorsal dural meninges, base of the brain, and around the spinal cord have each been implicated to have important roles in various CNS diseases. In this review, we discuss the contribution of meningeal lymphatics to these processes during both steady-state conditions and neuroinflammation, as well as discuss some of the many still unknown aspects regarding the role of meningeal lymphatics in neuroinflammation. Specifically, we focus on the observed phenomenon of lymphangiogenesis by a subset of meningeal lymphatics near the cribriform plate during neuroinflammation, and discuss their potential roles in immunosurveillance, fluid clearance, and access to the CSF and CNS compartments. We propose that manipulating CNS lymphatics may be a new therapeutic way to treat CNS infections, stroke, and autoimmunity.

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Section: Comparing Animal Models With Human Studiesmentioning

confidence: 99%

Neuroinflammation-Driven Lymphangiogenesis in CNS Diseases

Hsu

Laaker

Sándor

et al. 2021

Front. Cell. Neurosci.

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“…The lack of lymphatic vessels in the retina and brain presented a conceptual challenge in understanding how fluid homeostasis and the export of waste products are obtained within the confines of the CNS [ 1 ]. With the discovery of the glymphatic system initially in brains of rodents [ 2 , 3 , 4 , 5 ], and later in human brain by magnetic resonance imaging (MRI) studies [ 6 , 7 , 8 , 9 , 10 ], a glial-associated functional homologue of the lymphatic system was established. More recently, the existence of an ocular glymphatic clearance system was demonstrated [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Glymphatic System (En)during Inflammation

Mogensen

Delle

2021

IJMS

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The glymphatic system is a fluid-transport system that accesses all regions of the brain. It facilitates the exchange of cerebrospinal fluid and interstitial fluid and clears waste from the metabolically active brain. Astrocytic endfeet and their dense expression of the aquaporin-4 water channels promote fluid exchange between the perivascular spaces and the neuropil. Cerebrospinal and interstitial fluids are together transported back to the vascular compartment by meningeal and cervical lymphatic vessels. Multiple lines of work show that neurological diseases in general impair glymphatic fluid transport. Insofar as the glymphatic system plays a pseudo-lymphatic role in the central nervous system, it is poised to play a role in neuroinflammation. In this review, we discuss how the association of the glymphatic system with the meningeal lymphatic vessel calls for a renewal of established concepts on the CNS as an immune-privileged site. We also discuss potential approaches to target the glymphatic system to combat neuroinflammation.

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“…The latter is still a matter of debate. In a recent study, Melin et al [34] examined the efflux of intrathecal gadobutrol to nasal mucosa utilizing multi-phase, long-term MRI in humans. Despite a strong enrichment of CSF tracer in CSF spaces nearby the cribriform plate, there was no significant enrichment of CSF tracer in nasal mucosa, as measured in superior, medial and inferior turbinates, or in the nasal septum.…”

Section: Discussionmentioning

confidence: 99%

“…Despite a strong enrichment of CSF tracer in CSF spaces nearby the cribriform plate, there was no significant enrichment of CSF tracer in nasal mucosa, as measured in superior, medial and inferior turbinates, or in the nasal septum. Therefore, the authors questioned the importance of CSF drainage to the human nasal mucosa [34] . These study findings contradict the findings of other studies [18] , [35] .…”

Section: Discussionmentioning

confidence: 99%