Cotransporter-mediated water transport underlying cerebrospinal fluid formation

Steffensen, Annette Buur; Oernbo, Eva Kjer; Stoica, Anca; Gerkau, Niklas J.; Barbuskaite, Dagne; Tritsaris, Katerina; Rose, Christine R.; MacAulay, Nanna

doi:10.1038/s41467-018-04677-9

Cited by 141 publications

(258 citation statements)

References 67 publications

Supporting

Mentioning

235

Contrasting

Order By: Relevance

“…NKCC1 that is expressed in the apical membrane of CP may contribute as much as half of the CSF production, via ion-mediated cotransport of water [37,38].…”

Section: Cerebrospinal Fluid Production and Transport Systems In The mentioning

confidence: 99%

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

Solar

Zamani

Kubíčková

et al. 2020

Fluids Barriers CNS

160

132

View full text Add to dashboard Cite

The choroid plexus (CP) forming the blood-cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research. Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

show abstract

“…NKCC1 that is expressed in the apical membrane of CP may contribute as much as half of the CSF production, via ion-mediated cotransport of water [37,38].…”

Section: Cerebrospinal Fluid Production and Transport Systems In The mentioning

confidence: 99%

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

Solar

Zamani

Kubíčková

et al. 2020

Fluids Barriers CNS

160

132

View full text Add to dashboard Cite

show abstract

“…The total volume of CSF within adult humans is approximately 140 ml and the rate of secretion by each CP is 0.2 ml/min [12]. The pressure required for the circulation of CSF is maintained by a hydrostatic pressure gradient between the CP (where CSF is produced) and the arachnoid villi (where CSF is drained) [8].…”

Section: Open Accessmentioning

confidence: 99%

Cerebrospinal fluid dynamics modulation by diet and cytokines in rats

Alimajstorovic

Pascual-Baixauli

Hawkes

et al. 2020

Fluids Barriers CNS

View full text Add to dashboard Cite

Background: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by raised cerebrospinal fluid (CSF) pressure in the absence of any intracranial pathology. IIH mainly affects women with obesity between the ages of 15 and 45. Two possible mechanisms that could explain the increased CSF pressure in IIH are excessive CSF production by the choroid plexus (CP) epithelium or impaired CSF drainage from the brain. However, the molecular mechanisms controlling these mechanisms in IIH remain to be determined. Methods:In vivo ventriculo-cisternal perfusion (VCP) and variable rate infusion (VRI) techniques were used to assess changes in rates of CSF secretion and resistance to CSF drainage in female and male Wistar rats fed either a control (C) or high-fat (HF) diet (under anaesthesia with 20 μl/100 g medetomidine, 50 μl/100 g ketamine i.p). In addition, CSF secretion and drainage were assessed in female rats following treatment with inflammatory mediators known to be elevated in the CSF of IIH patients: C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1β, tumour necrosis factor-α (TNF-α), as well as glucocorticoid hydrocortisone (HC). Results:Female rats fed the HF diet had greater CSF secretion compared to those on control diet (3.18 ± 0.12 μl/ min HF, 1.49 ± 0.15 μl/min control). Increased CSF secretion was seen in both groups following HC treatment (by 132% in controls and 114% in HF) but only in control rats following TNF-α treatment (137% increase). The resistance to CSF drainage was not different between control and HF fed female rats (6.13 ± 0.44 mmH 2 O min/μl controls, and 7.09 ± 0.26 mmH 2 O min/μl HF). and when treated with CCL2, both groups displayed an increase in resistance to CSF drainage of 141% (controls) and 139% (HF) indicating lower levels of CSF drainage. Conclusions:Weight loss and therapies targeting HC, TNF-α and CCL2, whether separately or in combination, may be beneficial to modulate rates of CSF secretion and/or resistance to CSF drainage pathways, both factors likely contributing to the raised intracranial pressure (ICP) observed in female IIH patients with obesity.

show abstract

“…represents the net movement of sodium from blood to CSF, which is regulated by a variety of BCSFB sodium transporters such as Na + , K + -ATPase [36][37][38][39], ENaC [36,40] and NKCC1 [41].…”

Section: Discussionmentioning

confidence: 99%

“…It is not known how the expression levels of ENaC on the different membranes of BCSFB cells are affected by migraine triggers. The other main BCSFB sodium transporter is NKCC1, which can regulate CSF production [53] and sodium movement from blood to CSF [41]. Overall, sodium transport from blood to CSF across the BCSFB is regulated by a variety of transporters, channels and proteins, whose interactions with each other are not well understood.…”

Section: Discussionmentioning

confidence: 99%

Regulation of CSF and brain tissue sodium levels by the blood-CSF and blood-brain barriers during migraine

Ghaffari

Grant²,

Petzold

et al. 2019

Preprint

View full text Add to dashboard Cite

BackgroundCerebrospinal fluid (CSF) and brain tissue sodium levels increase during migraine. However, little is known regarding the underlying mechanisms of sodium homeostasis disturbance in the brain during the onset and propagation of migraine. Exploring the cause of sodium dysregulation in the brain is important, since correction of the altered sodium homeostasis could potentially treat migraine. Under the hypothesis that disturbances in sodium transport mechanisms at the blood-CSF barrier (BCSFB) and/or the blood-brain barrier (BBB) are the underlying cause of the elevated CSF and brain tissue sodium levels during migraines, we developed a mechanistic, differential equation model of a rat's brain to compare the significance of the BCSFB and the BBB in controlling CSF and brain tissue sodium levels. The model includes the ventricular system, subarachnoid space, brain tissue and blood. Sodium transport from blood to CSF across the BCSFB, and from blood to brain tissue across the BBB were modeled by influx permeability coefficients and , respectively, while sodium movement from CSF into blood across the BCSFB, and from brain tissue to blood across the BBB were modeled by efflux permeability coefficients ′ and ′ , respectively. We then performed a global sensitivity analysis to investigate the sensitivity of the ventricular CSF, subarachnoid CSF and brain tissue sodium concentrations to pathophysiological variations in , , ′ and ′ . Our results show that the ventricular CSF sodium concentration is highly influenced by perturbations of , and to a much lesser extent by perturbations of ′ . Brain tissue and subarachnoid CSF sodium concentrations are more sensitive to pathophysiological variations of and ′ than variations of and ′ within 30 minutes of the onset of the perturbations. However, is the most sensitive model parameter, followed by and ′ , in controlling brain tissue and subarachnoid CSF sodium levels within 2 hours of the perturbation onset.

show abstract

Cotransporter-mediated water transport underlying cerebrospinal fluid formation

Cited by 141 publications

References 67 publications

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

Cerebrospinal fluid dynamics modulation by diet and cytokines in rats

Regulation of CSF and brain tissue sodium levels by the blood-CSF and blood-brain barriers during migraine

Contact Info

Product

Resources

About