Aquaporin-4 expression in the cerebrospinal fluid in congenital human hydrocephalus

Castañeyra-Ruiz, Leandro; González-Marrero, Ibrahim; González-Toledo, Juan M.; Castañeyra-Ruiz, Agustín; Paz-Carmona, Héctor de; Castañeyra-Perdomo, Agustín; Carmona-Calero, Emilia M.

doi:10.1186/2045-8118-10-18

Cited by 39 publications

(29 citation statements)

References 23 publications

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“…Previous studies using PAGE/WB of CSF samples have used a variety of loading controls, including albumin [35], transthyretin [36], and transferrin [37]. Others have used no loading control or equal CSF volume loading [38, 39]. A validated loading control for CSF WB would improve the accuracy of the obtained results.…”

Section: Introductionmentioning

confidence: 99%

Total protein is an effective loading control for cerebrospinal fluid western blots

Collins

Peller

et al. 2015

Journal of Neuroscience Methods

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Background Cerebrospinal fluid (CSF) has been used to identify biomarkers of neurological disease. CSF protein biomarkers identified by high-throughput methods, however, require further validation. While Western blotting (WB) is well-suited to this task, the lack of a validated loading control for CSF WB limits the method’s accuracy. New Method We investigated the use of total protein (TP) as a CSF WB loading control. Using iodine-based reversible membrane staining, we determined the linear range and consistency of the CSF TP signal. We then spiked green fluorescent protein (GFP) into CSF to create defined sample-to-sample differences in GFP levels that were measured by WB before and after TP loading correction. Levels of CSF complement C3 and cystatin C measured by WB with TP loading correction and ELISA in amyotrophic lateral sclerosis and healthy control CSF samples were then compared. Results CSF WB with the TP loading control accurately detected defined differences in GFP levels and corrected for simulated loading errors. Individual CSF sample Western blot and ELISA measurements of complement C3 and cystatin C were significantly correlated and the methods showed a comparable ability to detect between-groups differences. Comparison with Existing Method CSF TP staining has a greater linear dynamic range and sample-to-sample consistency than albumin, a commonly used CSF loading control. The method accurately corrects for simulated errors in loading and improves the sensitivity of CSF WB compared to using no loading control. Conclusions The TP staining loading control improves the sensitivity and accuracy of CSF WB results.

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Section: Introductionmentioning

confidence: 99%

Total protein is an effective loading control for cerebrospinal fluid western blots

Collins

Peller

et al. 2015

Journal of Neuroscience Methods

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“…In humans, cortical brain biopsies from patients with chronic hydrocephalus showed increased AQP4 immunoreactivity compared with controls, with some loss of AQP4 polarization in astrocyte end feet [28] . One report found mildly ( ∼ 40%) increased AQP4 protein in CSF of congenital communicating hydrocephalus, suggesting ependymal denudation [29] . Most studies therefore report increased AQP4 expression associated with hydrocephalus, which could represent a compensatory response to increase brain water clearance.…”

Section: Aqp4 and Hydrocephalusmentioning

confidence: 99%

Aquaporin Water Channels and Hydrocephalus

Tradtrantip¹,

Smith²,

Yao³

2016

Pediatr Neurosurg

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The aquaporins (AQPs) are a family of water-transporting proteins that are broadly expressed in mammalian cells. Two AQPs in the central nervous system, AQP1 and AQP4, might play a role in hydrocephalus and are thus potential drug targets. AQP1 is expressed in the ventricular-facing membrane of choroid plexus epithelial cells, where it facilitates the secretion of cerebrospinal fluid (CSF). AQP4 is expressed in astrocyte foot processes and ependymal cells lining ventricles, where it appears to facilitate the transport of excess water out of the brain. Altered expression of these AQPs in experimental animal models of hydrocephalus and limited human specimens suggests their involvement in the pathophysiology of hydrocephalus, as do data in knockout mice demonstrating a protective effect of AQP1 deletion and a deleterious effect of AQP4 deletion in hydrocephalus. Though significant questions remain, including the precise contribution of AQP1 to CSF secretion in humans and the mechanisms by which AQP4 facilitates clearance of excess brain water, AQP1 and AQP4 have been proposed as potential drug targets to reduce ventricular enlargement in hydrocephalus.

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“…42 In contrast, ependymal AQP4 is upregulated in the late stages of hydrocephalus, possibly as a compen-satory mechanism to maintain water homeostasis. 19,86 In addition, it has been well documented that the ependymal cells lining the ventricular space have motile cilia and that defects in motile cilia lead to hydrocephalus. 6,84 Mice with mutations in the cilia proteins Spag6 or hydin, or the transcription factor Hfh4 (Foxj1, Mouse Genome Informatics) that lack ependymal cell cilia all exhibit hydrocephalus.…”

Section: Hydrocephalus and Csf Productionmentioning

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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Aquaporin-4 expression in the cerebrospinal fluid in congenital human hydrocephalus

Cited by 39 publications

References 23 publications

Total protein is an effective loading control for cerebrospinal fluid western blots

Total protein is an effective loading control for cerebrospinal fluid western blots

Aquaporin Water Channels and Hydrocephalus

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

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