Lymphatic Vessels Gain Access to Cerebrospinal Fluid Through Unique Association with Olfactory Nerves

Захаров, А. В.; Papaiconomou, Christina; Johnston, Mary

doi:10.1089/lrb.2004.2.139

Cited by 63 publications

(44 citation statements)

References 16 publications

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“…Application of immunohistochemistry for LYVE-1 to such specimens as tissue sections and blocks is useful for demonstrating the cranial lymphatic system in the murine cranium. The present histochemical findings in the nasal region indicate a possible drainage route for cerebrospinal fluid along the olfactory nerves in the mouse, as reported in the other mammals including sheep (9), pig (12), lamb (27) and rat (12,25). Our immunohistochemical examination further disclosed the lymphatic vessels in the dura mater on the cribriform plate within the murine neurocranium, thus implying that the cerebrospinal fluid drainage from the subarachnoidal space to the nasal lymphatics might-at least partly-commence with the intracranial dural lymphatics.…”

Section: Lymphatics In the Maxillary And Mandibular Regionsupporting

confidence: 84%

“…Several reports have described the lymphatic vessels associated with optic and olfactory nerves in the viscerocranial region of some mammals. The studies using injections of a silastic material such as Mirofil ® (MV-122; Flow Tech Inc., Carver, MA) and/or dyes into the subarachnoidal space have demonstrated the nasal lymphatic vessels, and this implies the cerebrospinal fluid drainage route along the olfactory nerves into the nasal lymphatics (9,12,25,27). Additionally in the optic nerve, the lymphatic vessels have been shown in the dura mater of the nerve sheath and thought to serve as drainage pathway of cerebrospinal fluid (5,6,11,14).…”

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confidence: 99%

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Topographic study on nerve-associated lymphatic vessels in the murine craniofacial region by immunohistochemistry and electron microscopy

et al. 2008

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The distribution and fine structure of lymphatic vessels associated with nerves was studied by immunohistochemistry in the murine craniofacial region. The tissue sections and blocks were immunostained for LYVE-1, protein gene product 9.5, CD34 and aquaporin-1 to demonstrate the lymphatic vessels, nerves, blood vessels and water channel protein, respectively. Transmission electron microscopic examination was also performed to investigate the relationship between the lymphatics and nerves. In the nasal area, the lymphatics were found in dura mater on the cribriform plate and beneath the nasal mucosa, this supposedly supplying the cerebrospinal fluid drainage route along the olfactory nerves. The proximal portions of the cranial nerves were equipped with the lymphatics in the epineurium. In the distal portions of the nerves, the lymphatics were distributed in close proximity of the perineural sheath, and thus might contribute to maintenance of microenvironment suitable for the nerves by an absorptive activity of the lymphatic endothelial cells. The present findings suggest that the lymphatic system associated with the cranial nerves provides the pathway for transport of cerebrospinal fluid, tissue fluid, and free cells involved in immune response and tumor metastasis in the craniofacial region.

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Section: Lymphatics In the Maxillary And Mandibular Regionsupporting

confidence: 84%

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confidence: 99%

Topographic study on nerve-associated lymphatic vessels in the murine craniofacial region by immunohistochemistry and electron microscopy

et al. 2008

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“…Substantial CtsD was also detected in liver, heart, and spleen so that a direct contribution of vasculature to distribution of CtsD cannot be ruled out, but lymphatics are draining into vasculature as well, leaving the relative contribution of both routes unclear. Given the forebrain injection of the viral vector, the olfactory nerve, which leaves the brain through the cribriform plate and through its perineural spaces provides direct continuity between subarachnoid space and olfactory sub mucosa lymphatics, 23 appears to be a good candidate for the route by which CtsD is drained from CNS to periphery. In any case, after CNS expression, CtsD appears to be targeted to sites within the organism that are not reached by visceral vector application despite the ubiquitous transduction.…”

Section: Discussionmentioning

confidence: 99%

CNS-Expressed Cathepsin D Prevents Lymphopenia in a Murine Model of Congenital Neuronal Ceroid Lipofuscinosis

Шевцова

Garrido

Weishaupt

et al. 2010

The American Journal of Pathology

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“…There were very good attempts for around the past two decades to distinguish which model was realistic. However, more recent data (in rat and other animal models, using microfilm as a contrast medium) suggests rather, that CSF-BISF could move directly from the subarachnoid space into submucosal lymphatics that emerge at the level of the cribriform plate, implying the clearance process is more efficient than that represented by Figure 6(C) [117] [118] [119] [120] [121]. During that time, the function of the glymphatic system (specified in later sub-sections) was not clearly understood.…”

Section: Endeavor To Understand Pathways For Lymphatic Drainage Of Csmentioning

confidence: 99%

The Integrative Five-Fluid Circulation System in the Human Body

Fung¹,

Kong²

2016

OJMIP

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Water is the key medium to transport numerous constituents and to provide a platform for physiological processes to take place in the living organisms in general; it also participates actively in many of these processes. In humans, there are different vehicles to contain water and its constituents. Our objective is to find out whether there is an overall water-base circulation system in the human body by analyzing the updated findings of different research groups on the physiological functions of various seemingly isolated fluid systems. By 1963, there were five separate fluid systems discovered in mammalians: (i) The Primo Vasculature Fluid (PVF) with protein precursors and micro cells held in the Primo Vasculature System (PVS). (ii) Blood with its constituents held in the cardio vasculature. (iii) Extracranial interstitial fluid (ISF) whose vehicle had a very irregular structure-the interstitium all over the body. (iv) The cerebrospinal fluid had been considered to be within the brain ventricles and spinal canal. (v) The extra-cranial lymphatic system which drained ISF, and had been known to join the subclavian vein. Fluid (i) was first reported in 1963 and fluids (ii) to (v) have been known for many decades, but the failure to detect a lymphatic system inside the skull has also been a mystery for many decades. The intra-cranial ISF (which we name as BISF) has drawn little attention, apart from discussing the mechanism of the blood-brain-barrier. During the past decade, there has been direct evidence indicating that CSF and BISF are actually mixed. After that, the intracranial lymphatic system was discovered and confirmed in animal models only slightly over one year back, and we called such fluid as glymphatic-fluid. After reviewing the stated "classical" five fluid systems together with the new findings in Sections 2 -7, we propose, for the first time, that the PVF, the blood, ISF, a mixture of CSF-BISF, and a mixture of glymphatic-fluid and lymph form an integrative circulation system in water base in the human and other mammalian bodies, as schematically represented in the last section. In this paper, we point out the positive correlation of chronic neuro degenerative diseases such as Alzheimer's disease, Parkinson's diseases and the insufficient brain wastes clearance by the glymphatic system. We also discuss the role played by the venous vessels as part of such clearance in upright posture. Moreover, simple non-invasive maneuver techniques are introduced here, as one example of enhancement of glymphatic fluid flow out of the skull to join the lymphatic system. A series of questions are raised in Section 8, the answers to which would help us to understand the transition from physio-to pathological states in the development of many diseases. Detailed analysis of this paper leads us to consider that research in understanding this integrative circulation system is only at the infancy stage, and fluid dynamics investigation seems to be the plausible modality of approach in the near future.

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Lymphatic Vessels Gain Access to Cerebrospinal Fluid Through Unique Association with Olfactory Nerves

Abstract: Lymphatic vessels gain access to the brain extracellular fluid (CSF) in an unusual anatomical association with the olfactory nerves external to the cranial vault. This study highlights the important role played by lymphatic vessels in CSF absorption.

Cited by 63 publications

References 16 publications

Topographic study on nerve-associated lymphatic vessels in the murine craniofacial region by immunohistochemistry and electron microscopy

Topographic study on nerve-associated lymphatic vessels in the murine craniofacial region by immunohistochemistry and electron microscopy

CNS-Expressed Cathepsin D Prevents Lymphopenia in a Murine Model of Congenital Neuronal Ceroid Lipofuscinosis

The Integrative Five-Fluid Circulation System in the Human Body

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