scholarly journals Aquaporin-4 Expression In The Human Choroid Plexus

2021 ◽  
Author(s):  
Felix Deffner ◽  
Corinna Gleiser ◽  
Ulrich Mattheus ◽  
Andreas Wagner ◽  
Peter H Neckel ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Mrna Level ◽  
Age Groups ◽  
Freeze Fracture ◽  
Aquaporin 4 ◽  
Ependymal Cells ◽  
Aqp4 Expression ◽  
Age Related

Abstract Background: The choroid plexus (CP) consists of specialized ependymal cells and underlying stroma and blood vessels, producing the bulk of the cerebrospinal fluid (CSF). CP epithelial cells are the site of the internal blood-cerebrospinal fluid barrier, show epithelial characteristics (basal lamina, tight junctions), and express aquaporin-1 (AQP1) apically. In contrast, ventricle-lining ependymal cells express aquaporin-4 (AQP4) basolaterallly. The initial purpose of this study was to analyze the expression of aquaporins in the ependyma – CP transition zone in the human brain to gain insights in aquaporin regulation. The results prompted us to investigate aquaporin expression in the mouse CP of different age groups. Methods: We analyzed the CP from eight body donors (age 74-91) applying immunofluorescence, qPCR, and freeze-fracture electron microscopy. We used antibodies against AQP1, AQP4, NKCC1, and Na/K-ATPase. In addition, we compared the CP from young (2 months), adult (12 months) and old (30 months) mice by qPCR and immunofluorescence. Results: Unexpectedly, many cells in the human CP were positive not only for AQP1 but also for AQP4, normally restricted to ependymal cells and astrocytes. Expression of AQP1 and AQP4 was found in the CP of all eight body donors. These results were confirmed by qPCR, and by electron microscopy detecting AQP4-specific orthogonal arrays of particles. To find out whether AQP4 expression correlated with relevant transport-related proteins we investigated expression of NKCC1 and Na/K-ATPase. Immunostaining for NKCC1 was similar to AQP1 and revealed no particular pattern related to AQP4. Co-staining of AQP4 and Na/K-ATPase indicated a trend for an inverse correlation of their expression. To test for the possibility of age-related changes causing AQP4 expression in the CP, we analyzed mouse brains from different age groups and found a significant increase of AQP4 on the mRNA level in old mice compared to young and adult animals. Conclusions: We provide evidence for AQP4 expression in the human and murine CP related to aging which likely contributes to the water flow through the CP epithelium and CSF production. In two alternative hypotheses, we discuss this as a beneficial compensatory, or a detrimental mechanism influencing the previously observed CSF changes during aging.

scholarly journals Aquaporin-4 Expression in the Human Choroid Plexus

2021 ◽  
Author(s):  
Felix Deffner ◽  
Corinna Gleiser ◽  
Ulrich Mattheus ◽  
Andreas Wagner ◽  
Peter H Neckel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Epithelial Cells ◽  
Choroid Plexus ◽  
Mrna Level ◽  
Inverse Correlation ◽  
Aquaporin 4 ◽  
Ependymal Cells ◽  
Aging Brain ◽  
Aqp4 Expression ◽  
Age Related

Abstract The choroid plexus (CP) consists of specialized ependymal cells and underlying blood vessels and stroma producing the bulk of the cerebrospinal fluid (CSF). CP epithelial cells are considered the site of the internal blood-cerebrospinal fluid barrier, show epithelial characteristics (basal lamina, tight junctions), and express aquaporin-1 (AQP1) apically. In this study, we analyzed the expression of aquaporins in the human CP using immunofluorescence and qPCR. As previously reported, AQP1 was expressed apically in CP epithelial cells. Surprisingly, and previously unknown, many cells in the CP epithelium were also positive for aquaporin-4 (AQP4), normally restricted to ventricle-lining ependymal cells and astrocytes in the brain. Expression of AQP1 and AQP4 was found in the CP of all eight body donors investigated (3 males, 5 females; age 74-91). These results were confirmed by qPCR, and by electron microscopy detecting orthogonal arrays of particles. To find out whether AQP4 expression correlated with the expression pattern of relevant transport-related proteins we also investigated expression of NKCC1, and Na/K-ATPase. Immunostaining with NKCC1 was similar to AQP1 and revealed no particular pattern related to AQP4. Co-staining of AQP4 and Na/K-ATPase indicated a trend for an inverse correlation of their expression. We hypothesized that AQP4 expression in the CP was caused by age-related changes. To address this, we investigated mouse brains from young (2 months), adult (12 months) and old (30 months) mice. We found a significant increase of AQP4 on the mRNA level in old mice compared to young and adult animals. Taken together, we provide evidence for AQP4 expression in the CP of the aging brain which likely contributes to the water flow through the CP epithelium and CSF production. In two alternative hypotheses, we discuss this as a beneficial compensatory, or a detrimental mechanism influencing the previously observed CSF changes during aging.

scholarly journals Cerebrospinal Fluid Protein Concentrations in Children: Age-related Values in Patients without Disorders of the Central Nervous System

2000 ◽  
Vol 46 (3) ◽  
pp. 399-403 ◽  
Author(s):  
Daniel Biou ◽  
Jean-François Benoist ◽  
Claire Nguyen-Thi ◽  
Xuan Huong ◽  
Philippe Morel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Reference Values ◽  
Total Protein ◽  
Age Groups ◽  
Term Neonates ◽  
Age Related ◽  
The Central Nervous System ◽  
Set Up ◽  
Age Range ◽  
Cerebrospinal Fluid Protein

Abstract Background: The published reference values for cerebrospinal fluid (CSF) total protein concentrations in children suffer from two major drawbacks: (a) the age-related range often is too broad when applied to the steeply falling concentrations in early infancy; and (b) no values have been published for widely used dry chemistry methods. Methods: We conducted a 2-year retrospective survey of CSF results obtained in a children’s hospital with a dry chemistry-based method set up on the Vitros 700 analyzer. Results: The data related to ambulatory children up to 16 years of age and term neonates with no clinical or biological signs of brain disease (n = 1074). Seven age groups with significantly different CSF protein values were identified, and their age-related percentiles (5th, 50th, and 95th) were determined. On the basis of the upper 95th percentile, from age 0 to 6 months the CSF protein concentrations fell rapidly from 1.08 to 0.40 g/L. A plateau (0.32 g/L) was reached from age 6 months to 10 years, followed by a slight increase (0.41 g/L) in the 10–16 years age range. Conclusions: These results imply that CSF total protein concentrations in the pediatric setting, particularly in infants, must always be interpreted with regard to narrow age-related reference values to avoid false-positive results.

Fine Structural Localization of Intravenously Injected Cytochrome C in the Porcine Choroid Plexus

1973 ◽  
Vol 31 ◽  
pp. 652-653
Author(s):  
D. A. Davis ◽  
T. H. Milhorat ◽  
B. J. Lloyd
Keyword(s):  
Electron Microscopy ◽  
Cerebrospinal Fluid ◽  
Cytochrome C ◽  
Horseradish Peroxidase ◽  
Choroid Plexus ◽  
Structural Localization

In the continuing search for suitable markers that can be used for examining mechanisms of cerebrospinal fluid (CSF) formation, we were recently led to a study of cytochrome c. This hemo-chromogen has two primary advantages as a marker: 1. It is g. considerably smaller protein (molecular wt. 13,000, radius 15 Å) than ferritin (molecular wt. 400,000, radius 5 Å) or horseradish peroxidase (molecular wt. 40,000, radius 25-30Å) ; 2. It is easily visualized by electron microscopy after reaction with 3,3'-diaminobenzidine (dab).Cytochrome c (Cal Biochem Grade A) was administered intravenously to pigs (7-9 kg. in wt.) in doses of 25-30 mg./100 g. wt.

Choroid plexus carcinoma in childhood: An Light and EM study

1991 ◽  
Vol 49 ◽  
pp. 98-99
Author(s):  
Maya Sasi ◽  
Joseph M Harb
Keyword(s):  
Choroid Plexus ◽  
Age Groups ◽  
Choroid Plexus Carcinoma ◽  
Ependymal Cells ◽  
Benign Tumors ◽  
Age Group ◽  
Electron Microscopic ◽  
Pediatric Age Group ◽  
Microscopic Features ◽  
Choroid Plexus Carcinomas

The normal choroid plexus consists of plexiform pial vessels covered by an epithelial layer which is modified from ependymal cells. Neoplasms of the choroid epithelial cells constitute less than 1% of intracranial neoplasms in all age groups and 2-5% in the pediatric age group. The choroid plexus tumors are divided into two categories, with the benign tumors known as the choroid plexus papillomas and their malignant counterparts being the choroid plexus carcinomas. Only 35 cases of choroid plexus carcinomas have been reported in the literature and only 9 of those included ultrastructural descriptions. In this report, we describe the light and electron microscopic features of three additional cases of this rare neoplasm.

Fine Structure of the Lateral Area of the Posterior Rhombencephalic Tela of the Bullfrog, Rana Catesbiana

1980 ◽  
Vol 38 ◽  
pp. 522-523
Author(s):  
J. E. Michaels ◽  
P. A. Tornheim
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Subarachnoid Space ◽  
Fourth Ventricle ◽  
Essential Feature ◽  
Ventricular System ◽  
Ependymal Cells ◽  
Open Communication ◽  
Tela Choroidea ◽  
Lateral Area

In mammals, the caudal roof of the fourth ventricle consists of an inner layer of ependymal cells and an outer layer of leptomeningeal cells. It contains specializations in the form of tufts of choroid plexus for the elaboration of cerebrospinal fluid (CSF) as well as gross apertures that permit open communication between the ventricular system and the subarachnoid space, an essential feature for mammalian CSF circulation. In the bullfrog, as in most submammals, the roof of the fourth ventricle contains a rostral rhombencephalic choroid plexus with no gross evidence of fourth ventricular apertures. Communication between the ventricular system and the subarachnoid space in this animal, however, has been demonstrated to occur by way of microscopic openings or pores in the caudal roof of the hindbrain or the posterior rhombencephalic tela choroidea.

Intracranial Pressure

2019 ◽  
pp. 69-73
Author(s):  
Eelco F. M. Wijdicks ◽  
William D. Freeman
Keyword(s):  
Cerebrospinal Fluid ◽  
Smooth Muscle ◽  
Choroid Plexus ◽  
Blood Cells ◽  
White Blood Cells ◽  
Ependymal Cells ◽  
Cerebral Aqueduct ◽  
Epithelial Surface ◽  
The Brain ◽  
Route Of Delivery

Cerebrospinal fluid (CSF) fills the subarachnoid space, spinal canal, and ventricles of the brain. CSF is enclosed within the brain by the pial layer, ependymal cells lining the ventricles, and the epithelial surface of the choroid plexus, where it is largely produced. Choroid plexus is present throughout the ventricular system with the exception of the frontal and occipital horns of the lateral ventricle and the cerebral aqueduct. The vascular smooth muscle and the epithelium of the choroid plexus receive both sympathetic and parasympathetic input. In an adult, CSF is normally acellular. A normal spinal sample may contain up to 5 white blood cells (WBCs) or red blood cells (RBCs). CSF allows for a route of delivery and removal of nutrients, hormones, and transmitters for the brain.

Scanning Electron Microscopy of the Choroid Plexus and Ventricular Wall Ependyma in the Rhesus Monkey

1971 ◽  
Vol 29 ◽  
pp. 270-271
Author(s):  
Philip P. McGrath ◽  
Ronald G. Clark ◽  
John B. Ewell ◽  
John M. Wehrung
Keyword(s):  
Electron Microscopy ◽  
Electron Microscope ◽  
Scanning Electron Microscope ◽  
Choroid Plexus ◽  
Ependymal Cell ◽  
Brain Parenchyma ◽  
Ependymal Cells ◽  
Apical Surface ◽  
Lateral Ventricles ◽  
Scanning Electron

The lumen of the lateral ventricles is separated from the brain parenchyma and the circulatory system by a single layer of specialized epithelial cells, the ependyma. This ependyma is divided into choroid plexus ependymal cells, which coat the pia arachnoid invagination in the lateral ventricles, and the wall ependymal cells which separate the lateral ventricle lumen from brain parenchyma. Using transmission electron microscopy, the ultrastructure of these cells has been described with special emphasis on the difference in apical surface membranes. The apical surface of the choroid plexus ependymal cell contains numerous microvilli and an occasional cilia while the wall ependymal cell contains numerous cilia and only a few microvilli. By scanning electron microscope we have demonstrated differences in the apical surface membrane.The specimens were fixed in glutaraldehyde by vascular perfusion or infusion into the ventricles and postfixed in osmium tetroxide. They were rinsed in cacodylate buffer and three changes of distilled water, blotted dry, and freeze dried, using liquid nitrogen. They were coated with gold palladium and examined in a Cambridge Mark II A stereoscan, scanning electron microscope.

scholarly journals Toward a better understanding of the cellular basis for cerebrospinal fluid shunt obstruction: report on the construction of a bank of explanted hydrocephalus devices

2016 ◽  
Vol 18 (2) ◽  
pp. 213-223 ◽  
Author(s):  
Brian W. Hanak ◽  
Emily F. Ross ◽  
Carolyn A. Harris ◽  
Samuel R. Browd ◽  
William Shain
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Calcium Binding ◽  
Cellular Response ◽  
Ependymal Cells ◽  
Ventricular Catheter ◽  
Cell Type ◽  
Ventricular Catheters ◽  
The Mean ◽  
Shunt Obstruction

OBJECTIVE Shunt obstruction by cells and/or tissue is the most common cause of shunt failure. Ventricular catheter obstruction alone accounts for more than 50% of shunt failures in pediatric patients. The authors sought to systematically collect explanted ventricular catheters from the Seattle Children's Hospital with a focus on elucidating the cellular mechanisms underlying obstruction. METHODS In the operating room, explanted hardware was placed in 4% paraformaldehyde. Weekly, samples were transferred to buffer solution and stored at 4°C. After consent was obtained for their use, catheters were labeled using cell-specific markers for astrocytes (glial fibrillary acidic protein), microglia (ionized calcium-binding adapter molecule 1), and choroid plexus (transthyretin) in conjunction with a nuclear stain (Hoechst). Catheters were mounted in custom polycarbonate imaging chambers. Three-dimensional, multispectral, spinning-disk confocal microscopy was used to image catheter cerebrospinal fluid–intake holes (10× objective, 499.2-μm-thick z-stack, 2.4-μm step size, Olympus IX81 inverted microscope with motorized stage and charge-coupled device camera). Values are reported as the mean ± standard error of the mean and were compared using a 2-tailed Mann-Whitney U-test. Significance was defined at p < 0.05. RESULTS Thirty-six ventricular catheters have been imaged to date, resulting in the following observations: 1) Astrocytes and microglia are the dominant cell types bound directly to catheter surfaces; 2) cellular binding to catheters is ubiquitous even if no grossly visible tissue is apparent; and 3) immunohistochemical techniques are of limited utility when a catheter has been exposed to Bugbee wire electrocautery. Statistical analysis of 24 catheters was performed, after excluding 7 catheters exposed to Bugbee wire cautery, 3 that were poorly fixed, and 2 that demonstrated pronounced autofluorescence. This analysis revealed that catheters with a microglia-dominant cellular response tended to be implanted for shorter durations (24.7 ± 6.7 days) than those with an astrocyte-dominant response (1183 ± 642 days; p = 0.027). CONCLUSIONS Ventricular catheter occlusion remains a significant source of shunt morbidity in the pediatric population, and given their ability to intimately associate with catheter surfaces, astrocytes and microglia appear to be critical to this pathophysiology. Microglia tend to be the dominant cell type on catheters implanted for less than 2 months, while astrocytes tend to be the most prevalent cell type on catheters implanted for longer time courses and are noted to serve as an interface for the secondary attachment of ependymal cells and choroid plexus.

scholarly journals Targeting the Choroid Plexuses for Protein Drug Delivery

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 963
Author(s):  
Mark A. Bryniarski ◽  
Tianjing Ren ◽  
Abbas R. Rizvi ◽  
Anthony M. Snyder ◽  
Marilyn E. Morris
Keyword(s):  
Drug Delivery ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Choroid Plexus ◽  
Protein Therapeutics ◽  
Ventricular System ◽  
Ependymal Cells ◽  
Choroid Plexuses ◽  
Choroid Plexus Epithelial

Delivery of therapeutic agents to the central nervous system is challenged by the barriers in place to regulate brain homeostasis. This is especially true for protein therapeutics. Targeting the barrier formed by the choroid plexuses at the interfaces of the systemic circulation and ventricular system may be a surrogate brain delivery strategy to circumvent the blood-brain barrier. Heterogenous cell populations located at the choroid plexuses provide diverse functions in regulating the exchange of material within the ventricular space. Receptor-mediated transcytosis may be a promising mechanism to deliver protein therapeutics across the tight junctions formed by choroid plexus epithelial cells. However, cerebrospinal fluid flow and other barriers formed by ependymal cells and perivascular spaces should also be considered for evaluation of protein therapeutic disposition. Various preclinical methods have been applied to delineate protein transport across the choroid plexuses, including imaging strategies, ventriculocisternal perfusions, and primary choroid plexus epithelial cell models. When used in combination with simultaneous measures of cerebrospinal fluid dynamics, they can yield important insight into pharmacokinetic properties within the brain. This review aims to provide an overview of the choroid plexuses and ventricular system to address their function as a barrier to pharmaceutical interventions and relevance for central nervous system drug delivery of protein therapeutics. Protein therapeutics targeting the ventricular system may provide new approaches in treating central nervous system diseases.

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