Integration of the subarachnoid space and lymphatics: Is it time to embrace a new concept of cerebrospinal fluid absorption?

Koh, Lena; Захаров, А. В.; Johnston, Mary

doi:10.1186/1743-8454-2-6

Cited by 231 publications

(173 citation statements)

References 88 publications

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“…Also, in monkeys, lymphatic vessels have been observed in spinal epidural tissues [126]. Since there is no direct evidence supporting direct spinal CSF-BISFlymph connections so far, it appears that CSF-BISF from the spinal subarachnoid compartment first passes into the epidural tissues from which absorption takes place into blind ending lymphatic vessels ( [116] Figures 1E-1F). Quantitatively, studies employing sheep model showed that the relative proportion of CSF absorption by the spinal compartment amounts to about 25% of total CSF-BISF clearance [127].…”

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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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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“…CSF drainage occurs directly into the blood via arachnoid villi or granulations into the venous sinuses of the dura mater and also into the lymphatic system via cranial and spinal nerves [138]. Drainage occurs along the olfactory nerves to the nasal mucosa to the cervical lymph nodes [16,17,59,101,172,188] and along spinal nerves to cervical, intercostal, and other lymph nodes [103]. An additional pathway for CSF/ISF drainage appears to occur within dural lymphatic vessels to the cervical lymph nodes [7,113], but just how CSF enters the dural lymphatic vessels has not been well described.…”

Section: Csf and Isf Compartmentalization And Drainage Pathwaysmentioning

confidence: 99%

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

et al. 2018

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Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K + , Ca 2+ , and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces. However, recent evidence favours important amendments to the 'glymphatic' hypothesis, particularly concerning the role of glia and transfer of solutes within the ECS. This review discusses studies which question the role of AQP4 in ISF flow and the lack of evidence for its ability to transport solutes; summarizes attributes of brain ECS that strongly favour the diffusion of small and large molecules without ISF flow; discusses work on hydraulic conductivity and the nature of the extracellular matrix which may impede fluid movement; and reconsiders the roles of the perivascular space (PVS) in CSF-ISF exchange and drainage. We also consider the extent to which CSF-ISF exchange is possible and desirable, the impact of neuropathology on fluid drainage, and why using CSF as a proxy measure of brain components or drug delivery is problematic. We propose that new work and key historical studies both support the concept of a perivascular fluid system, whereby CSF enters the brain via PVS convective flow or dispersion along larger caliber arteries/arterioles, diffusion predominantly regulates CSF/ISF exchange at the level of the neurovascular unit associated with CNS microvessels, and, finally, a mixture of CSF/ISF/waste products is normally cleared along the PVS of venules/veins as well as other pathways; such a system may or may not constitute a true 'circulation', but, at the least, suggests a comprehensive re-evaluation of the previously proposed 'glymphatic' concepts in favour of a new system better taking into account basic cerebrovascular physiology and fluid transport considerations.

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“…5), no CSF flow from the foramen of Monro to the lateral ventricles was detected. The lack of CSF flow at the level of the aqueduct, and clinical symptoms by increased intracranial pressure support the existence of additional flow paths 19,20 . The contrasting characteristics of CSF flow in the lateral ventricles of these patients suggest that time-SLIP CSF imaging can be used to characterize the pathophysiology of CSF dynamics.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Cerebrospinal Fluid Flow Patterns Using the Time-Spatial Labeling Inversion Pulse Technique with 3T MRI: Early Clinical Experiences

et al. 2014

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SUMMARY -CSF imaging using the time-spatial labeling inversion pulse (time-SLIP) technique at 3T magnetic resonance imaging (MRI) was performed to assess cerebrospinal fluid (CSF) dynamics. The study population comprised 15 healthy volunteers and five patients with MR findings showing expansive dilation of the third and lateral ventricles suggesting aqueductal stenosis (AS). Signal intensity changes were evaluated in the tag-labeled CSF, untagged brain parenchyma, and untagged CSF of healthy volunteers by changing of black-blood time-inversion pulse (BBTI

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Integration of the subarachnoid space and lymphatics: Is it time to embrace a new concept of cerebrospinal fluid absorption?

Cited by 231 publications

References 88 publications

The Integrative Five-Fluid Circulation System in the Human Body

The Integrative Five-Fluid Circulation System in the Human Body

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

Assessment of Cerebrospinal Fluid Flow Patterns Using the Time-Spatial Labeling Inversion Pulse Technique with 3T MRI: Early Clinical Experiences

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