A balanced view of choroid plexus structure and function: Focus on adult humans

Spector, Reynold; Keep, Richard F.; Snodgrass, S. Robert; Smith, Quentin R.; Johanson, Conrad E.

doi:10.1016/j.expneurol.2015.02.032

Cited by 181 publications

(187 citation statements)

References 93 publications

(158 reference statements)

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“…Contributing to this rhythm, respiration adds to pulsatility, but at a lower frequency [54]. Spector et al [166] suggest that during anaesthesia, with slower and shallower breathing, this mixing effect would be reduced.…”

Section: Pulsatile Flow Of Csfmentioning

confidence: 99%

“…Overall, the net CSF flow in adults is through the ventricles to the basal subarachnoid spaces [12,166].…”

Section: Pulsatile Flow Of Csfmentioning

confidence: 99%

“…All these will affect CSF flow and/or production, potentially influencing data obtained (these and other confounding factors are discussed in detail elsewhere [166]). Sampling CSF multiple times is a particular problem when comparing healthy and diseased states, or young versus old.…”

Section: Practical and Clinical Implications Of Isf/csf Interactionmentioning

confidence: 99%

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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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Section: Pulsatile Flow Of Csfmentioning

confidence: 99%

“…Overall, the net CSF flow in adults is through the ventricles to the basal subarachnoid spaces [12,166].…”

Section: Pulsatile Flow Of Csfmentioning

confidence: 99%

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

et al. 2018

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“…While studies involving the CSF have identified many potential ALS biomarkers, mass transfer occurs between the blood and CSF at the blood-CSF barrier, predominantly in the subarachnoid space and the choroid plexus [130,131], suggesting that the same biomarkers could be present in both fluid types. This was previously demonstrated where several studies have indicated significantly high correlations between blood (serum and plasma) and CSF levels of the same biomarker [34,38,44,118].…”

Section: Biomarkers In Blood (Serum and Plasma)mentioning

confidence: 99%

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Bowser

2017

Neurotherapeutics

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Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease with no effective treatment. Drug development has been hampered by the lack of biomarkers that aid in early diagnosis, demonstrate target engagement, monitor disease progression, and can serve as surrogate endpoints to assess the efficacy of treatments. Fluid-based biomarkers may potentially address these issues. An ideal biomarker should exhibit high specificity and sensitivity for distinguishing ALS from control (appropriate disease mimics and other neurologic diseases) populations and monitor disease progression within individual patients. Significant progress has been made using cerebrospinal fluid, serum, and plasma in the search for ALS biomarkers, with urine and saliva biomarkers still in earlier stages of development. A few of these biomarker candidates have demonstrated use in patient stratification, predicting disease course (fast vs slow progression) and severity, or have been used in preclinical and clinical applications. However, while ALS biomarker discovery has seen tremendous advancements in the last decade, validating biomarkers and moving them towards the clinic remains more elusive. In this review, we highlight biomarkers that are moving towards clinical utility and the challenges that remain in order to implement biomarkers at all stages of the ALS drug development process.

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“…28,29 The fenestrated capillaries of the choroid plexus are leaky and, in contrast to cerebral endothelia, readily allow the passage of ions and other small molecules. 5,121,124,146 The choroid plexus was first suggested as a site of CSF secretion by Faivre in 1854 41 and by Cushing in 1914, 25 and in 1960, De Rougemont et al 33 provided the first direct experimental evidence of choroid plexus-dependent CSF secretion. Although the theory is controversial, according to most models, the choroid plexus epithelium (CPE) generates a significant fraction, if not the majority, of CSF.…”

Section: Mechanisms Of Csf Secretionmentioning

confidence: 99%

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

Karimy¹,

Durán²,

Hu³

et al. 2016

FOC

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Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

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A balanced view of choroid plexus structure and function: Focus on adult humans

Cited by 181 publications

References 93 publications

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

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

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

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