Water and solute secretion by the choroid plexus

Prætorius, Jeppe

doi:10.1007/s00424-006-0170-6

Cited by 98 publications

(103 citation statements)

References 107 publications

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“…mouse, CSF from the subarachnoid space rapidly enters the brain via the Virchow-Robin spaces, along para-arterial channels to exchange with the ISF compartment (6). Such an extensive "retrograde" flux of CSF into the brain parenchyma is contrary to the classical model of CSF secretion and reabsorption (1,2). In this study, our first goal was to determine whether the paravascular influx of CSF into the brain could be observed by contrast-enhanced MRI following intrathecal delivery of different paramagnetic contrast agents.…”

Section: Introductionmentioning

confidence: 97%

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Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

et al. 2013

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The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain. IntroductionIn the classical model, cerebrospinal fluid (CSF) is actively secreted by the choroid plexus of the cerebral ventricles and travels by bulk or pulsatile flow through the ventricular system, flowing from the fourth ventricle into the subarachnoid space through the foramina of Luschka and the foramen of Magendie. From the subarachnoid space, CSF is thought to be reabsorbed into the blood stream either via arachnoid granulations of the dural sinuses or by passing out of the cranial cavity along cranial nerve sheathes to be eliminated through the cervical lymphatics (1, 2). Fluid movement along this CSF column is commonly measured by MRI. Phase-contrast MRI allows the visualization of CSF flow dynamics and is used clinically in the evaluation of communicating versus noncommunicating hydrocephalus, normal pressure hydrocephalus, and arachnoid cysts (3). Contrast-enhanced magnetic resonance cisternography can also be used to identify CSF leaks in the treatment of spontaneous intracranial hypotension or CSF rhinorrhea (4,5).In a recent study (6), we reported that, contrary to the textbook model of CSF secretion and reabsorption, a large proportion of subarachnoid CSF recirculates through the brain parenchyma along paravascular spaces and exchanges with the interstitial fluid (ISF) (a process referred to herein as CSF-ISF exchange). The flow of fluid along these paravascular routes and through the interstitium is supported by transglial water movement through astrocytic aquaporin-4 (AQP4) water channels and facilitates the efficient clearance of interstitial solutes, including soluble amyloid...

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Section: Introductionmentioning

confidence: 97%

“…From the subarachnoid space, CSF is thought to be reabsorbed into the blood stream either via arachnoid granulations of the dural sinuses or by passing out of the cranial cavity along cranial nerve sheathes to be eliminated through the cervical lymphatics (1,2). Fluid movement along this CSF column is commonly measured by MRI.…”

Section: Introductionmentioning

confidence: 99%

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

et al. 2013

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“…9 -11 Blockade of the sodium hydrogen exchanger (NHE) was first thought to be responsible for this, but NHE proteins are almost undetectable in the CP of rats. 5,12 Amiloride also blocks epithelial sodium channels (ENaCs), which we reported recently to be present in the CP of rats. 13 ENaCs are members of the amiloride-sensitive Na ϩ channels with 3 subunits, ␣, ␤, and ␥, forming a heteromultimeric Na ϩ channel in many transporting epithelia.…”

mentioning

confidence: 99%

“…3,4 The epithelium of the choroid plexus (CP) is the major site for production of CSF, which is later absorbed by arachnoid granulations. 5,6 Net transport of Na ϩ between plasma and CSF is a balance of Na ϩ influx into and efflux out of the CP cells, which is accomplished by selective distribution and activity of a variety of enzymes and transporters. 7,8 An increase in CSF [Na ϩ ] in Dahl S rats on a high-salt diet may, thus, be attributed to an increased efflux of Na ϩ into the CSF, decreased reuptake of Na ϩ from the CSF, or both.…”

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confidence: 99%

Sodium Transport in the Choroid Plexus and Salt-Sensitive Hypertension

et al. 2009

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Abstract-To elucidate the role of epithelial sodium channels (ENaCs) and Na ϩ -K ϩ -ATPase in Na ϩ transport by the choroid plexus, we studied ENaC expression and Na ϩ transport in the choroid plexus. Lateral ventricle choroid plexuses were obtained from young male Wistar, Dahl salt-resistant (SS.BN13), and Dahl salt-sensitive (SS/MCW) rats on a regular (0.3%) or high-(8.0%) salt diet. The effects of ENaC blocker benzamil and Na ϩ -K ϩ -ATPase blocker ouabain on sodium transport were evaluated by measuring the amounts of retained 22 Na ϩ and by evaluating intracellular [Na ϩ ] with Sodium Green fluorescence. In Wistar rats, ENaC distribution was as follows: microvilli, 10% to 30%; cytoplasm, 60% to 80%; and basolateral membrane, 5% to 10%. Benzamil (10 Ϫ8 Key Words: sodium Ⅲ choroid plexus Ⅲ ENaC Ⅲ Na ϩ -K ϩ -ATPase Ⅲ Dahl rats Ⅲ hypertension S trict regulation of [Na ϩ ] in the cerebrospinal fluid (CSF) and, thus, the central nervous system is crucial for normal functioning of neurons. An increase in CSF [Na ϩ ] by as little as 2 mmol/L can increase the firing rate of neurons. 1,2 A chronic 5-mmol/L increase in CSF [Na ϩ ] causes sympathetic hyperactivity and hypertension. 3 Such a subtle increase in CSF [Na ϩ ] might be a primary abnormality in salt-induced hypertension. CSF [Na ϩ ] increases by Յ5 mmol/L in Dahl salt-sensitive (S) rats and spontaneously hypertensive rats on a high-salt diet, and this increase appears to precede the increase in blood pressure, whereas CSF [Na ϩ ] shows minimal changes in "salt-resistant" strains, such as Wistar-Kyoto and Dahl salt-resistant (R) rats. 3,4 The epithelium of the choroid plexus (CP) is the major site for production of CSF, which is later absorbed by arachnoid granulations. 5,6 Net transport of Na ϩ between plasma and CSF is a balance of Na ϩ influx into and efflux out of the CP cells, which is accomplished by selective distribution and activity of a variety of enzymes and transporters. 7,8 An increase in CSF [Na ϩ ] in Dahl S rats on a high-salt diet may, thus, be attributed to an increased efflux of Na ϩ into the CSF, decreased reuptake of Na ϩ from the CSF, or both. However, the actual mechanisms contributing to the increase in CSF [Na ϩ ] in Dahl S rats or spontaneously hypertensive rats on a high-salt diet have not yet been studied.MA number of Na ϩ transporters mediate Na ϩ influx into the CP. On the basis of their distribution either on the apical or the basolateral surface, they contribute to the transport of Na ϩ from CSF or plasma into the CP cells along a prevailing electrochemical gradient. The Na ϩ channel blocker, amiloride, decreases Na ϩ transport into the CP and CSF. 9 -11 Blockade of the sodium hydrogen exchanger (NHE) was first thought to be responsible for this, but NHE proteins are almost undetectable in the CP of rats. 5,12 Amiloride also blocks epithelial sodium channels (ENaCs), which we reported recently to be present in the CP of rats. 13 ENaCs are members of the amiloride-sensitive Na ϩ channels with 3 subunits, ␣, ␤, and ␥, forming a ...

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“…23,28,110 However, many of the important hormones and their receptors that regulate systemic NaCl and water homeostasis, including aldosterone, angiotensin II, and vasopressin, are expressed in the CPE and ependyma also and likely play local roles in the CPE with respect to CSF production and brain extracellular fluid-volume regulation.…”

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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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Water and solute secretion by the choroid plexus

Cited by 98 publications

References 107 publications

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

Sodium Transport in the Choroid Plexus and Salt-Sensitive Hypertension

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

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