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PubMed1983

Characterization of lactogen binding sites in choroid plexus.

Prolactin binding sites have been demonstrated previously in rat choroid plexus using in vivo radioautography (Walsh et al. 1978). In the present study we have employed this procedure to characterize further the binding specificity of these sites. Following the injection of 125I-hGH or 125I-oPRL an intense radioautographic reaction was observed over the choroid plexus. The reaction was significantly reduced by coinjecting excess unlabeled hGH or oPRL but not bGH. The specific binding of 125I-oPRL to choroid plexus from rat, rabbit, sheep and pig was demonstrated by in vitro assays. Subsequently a survey of 125I-oPRL specific binding in a number of regions of pig brain indicated that the highest binding was in choroid plexus. A detailed study of the characteristics of 125I-oPRL binding to pig choroid plexus was undertaken. Specific binding increased with choroid plexus homogenate protein to a maximum of 30% (3.0 mg protein/tube). Binding was maximum at 4 degrees C by 30-40 h of incubation. During the incubation the integrity of 125I-oPRL in the incubation medium declined steadily to 50% after 20 h and 35-40% after 48 h. Radioactivity eluted from binding sites was fully intact as judged by rebinding to lactogen receptor-enriched membranes. Binding showed a broad pH optimum of 5.5-7.5. On cell fractionation of choroid plexus binding sites were enriched in microsomes. The binding of 125I-oPRL and 125I-hGH was inhibited in a dose-dependent manner by unlabeled lactogens and was of high affinity. hGH and oPRL were equipotent inhibitors of the binding of both radioligands whereas bGH and a variety of structurally unrelated peptides were non-inhibitory.

Animals↗

PubMed1992

Protein synthesis at the blood-brain barrier. The major protein secreted by amphibian choroid plexus is a lipocalin.

Among the proteins secreted by choroid plexus of vertebrates, one protein is much more abundant than all others. In mammals, birds, and reptiles this protein is transthyretin, a tetramer of identical 15-kDa subunits. In this study choroid plexus from frogs, tadpoles, and toads incubated in vitro were found to synthesize and secrete one predominant protein. However, this consisted of one single 20-kDa polypeptide chain. It was expressed throughout amphibian metamorphosis. Part of its amino acid sequence was determined and used for construction of oligonucleotides for polymerase chain reaction. The amplified DNA was used to screen a toad choroid plexus cDNA library. Full-length cDNA clones were isolated and sequenced. The derived amino acid sequence for the encoded protein was 183 amino acids long, including a 20-amino acid presegment. The calculated molecular weight of the mature protein was 18,500. Sequence comparison with other proteins showed that the protein belonged to the lipocalin superfamily. Its expression was highest in choroid plexus, much lower in other brain areas, and absent from liver. Since no transthyretin was detected in proteins secreted from amphibian choroid plexus, abundant synthesis and secretion of transthyretin in choroid plexus must have evolved only after the stage of the amphibians.

Amino Acid Sequence↗

PubMed1989

Uptake and concentrations of calcium in rat choroid plexus during chronic hypo- and hypercalcemia.

The choroid plexus has been implicated in the regulation of cerebrospinal fluid (CSF) [Ca], but little information is available concerning Ca transport by this epithelium. We determined the transfer coefficients for 45Ca uptake into choroid plexus from blood, as well as tissue [Ca], in weanling Fischer-344 rats fed low, normal, or high Ca diets for 8 weeks. Plasma [Ca] decreased by 45% with low Ca diet and increased by 25% with high Ca diet. Choroid plexus 45Ca uptake varied inversely with plasma [Ca]. This relation was due largely to changes in extracellular Ca binding rather than to entry from blood, as the transfer coefficient was independent of plasma [Ca]. The extracellular Ca distribution in choroid plexus, the intercept of a plot of tissue 45Ca distribution against time, was reciprocally related to plasma [Ca]. Changes in total cell [Ca] during hypercalcemia were equivalent to those in plasma, and in hypocalcemia were 70% of those in plasma. These findings indicate that regulation of CSF [Ca] does not involve saturable transport of Ca into the choroid epithelium from blood, and that the apical membrane of the choroid epithelium is involved in homeostasis of CSF [Ca].

Animals↗

PubMed1986

Intermediate filament proteins in choroid plexus and ependyma and their tumors.

The intermediate filament protein types of normal choroid plexus and ependymal tissue and their putative tumors were investigated. In normal human choroid plexus tissue, but not in ependyma, keratin could be demonstrated immunohistochemically. By immunoblotting, keratins 8, 18, and 19 were found, but glial fibrillary acidic protein (GFAP) was absent. In mouse and rat, choroid plexus epithelium and ependymal lining cells were keratin-positive. In addition, many ependymal cells were vimentin-positive. Keratin was immunohistochemically found in three of four choroid plexus papillomas, two of two choroid plexus carcinomas, and the lining cells of three neuroepithelial cysts. GFAP-positive cells were present in some choroid plexus tumors. In contrast, none of the eight ependymomas contained keratin, but all were strongly positive for GFAP. The results show that choroid plexus lining cells and choroid plexus tumors have true epithelial characteristics in their cytoskeleton, in contrast to ependymomas, which do not show keratin positivity but show glial filaments, as would be seen in astrocytic tumors.

Adult↗

PubMed1991

Kinetics of circulating vasopressin uptake by choroid plexus.

Uptake of circulating arginine vasopressin (AVP) by choroid plexus was studied by means of the in situ brain perfusion technique in anesthetized guinea pig and by means of single-circulation paired-tracer dilution technique in isolated perfused sheep choroid plexus. Kinetic analysis revealed saturable AVP uptake with Michaelis constant (Km) values of 32 +/- 4 and 31 +/- 5 nM and maximal saturable influx rate (Vmax) of 0.45 +/- 0.06 and 12.1 +/- 0.67 pmol.min-1.g-1 in guinea pig and sheep choroid plexus, respectively. The peptide fragments AVP-(1-8) and [pGlu4,Cyt6]AVP-(4-9), the amino acids L-phenylalanine, L-tyrosine, and 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid, and the aminopeptidase inhibitors Bestatin and bacitracin did not influence hormone kinetics. However, the V1 antagonist [(1-beta-mercapto-beta,beta-cyclo-pentamethylenepropionic acid)-O-methyl-Tyr2]AVP significantly inhibited AVP uptake with inhibitor constant (Ki) values of 0.19 +/- 0.03 (guinea pig) and 0.07 +/- 0.01 microM (sheep). The V2 agonist 1-desamino-8-D-AVP and pressinoic acid produced weak inhibitions only in guinea pig choroid plexus, and Ki/Km ratios indicated 220 and 310 times lower affinities than for AVP, respectively. It is suggested that the membrane mechanism responsible for AVP uptake in choroid plexus has a binding site with properties similar to those of V1 receptor.

Animals↗

PubMed1986

Nucleoside transporter of cerebral microvessels and choroid plexus.

The nucleoside transporter of cerebral microvessels and choroid plexus was identified and characterized using [3H]nitrobenzylthioinosine (NBMPR) as a specific probe. [3H]NBMPR bound reversibly and with high affinity to a single specific site in particulate fractions of cerebral microvessels, choroid plexus, and cerebral cortex of the rat and the pig. The dissociation constants (KD 0.1-0.7 nM) were similar in the various tissue preparations from each species, but the maximal binding capacities (Bmax) were about fivefold higher in cerebral microvessels and choroid plexus than in the cerebral cortex. Nitrobenzylthioguanosine and dipyridamole were the most potent competitors for [3H]NBMPR binding. Several naturally occurring nucleosides displaced specific [3H]NBMPR binding to cerebral microvessels in vitro, in a rank order that correlated well with their ability to cross the blood-brain barrier in vivo. Adenosine analogues and theophylline were less effective in displacing [3H]NBMPR binding than in displacing adenosine receptor ligands. Photoactivation of cerebral microvessels and choroid plexus bound with [3H]NBMPR followed by solubilization and polyacrylamide gel electrophoresis labeled a protein(s) with a molecular weight of approximately 60,000. These results indicate that cerebral microvessels and choroid plexus have a much higher density of the nucleoside transporter moiety than the cerebral cortex and that this nucleoside transporter has pharmacological properties and a molecular weight similar to those of erythrocytes and other mammalian tissues.

Adenosine↗

PubMed1992

Flow cytometric analysis of deoxyribonucleic acid ploidy and proliferation in choroid plexus tumors.

The deoxyribonucleic acid (DNA) content of 10 choroid plexus tumors, including 4 malignant tumors and 3 normal choroid plexus controls, was analyzed by flow cytometry to determine whether a ploidy or proliferation rate is a better predictor of tumor behavior than histological features. Nine of 10 neoplasms had both diploid and aneuploid modal populations. One neoplasm and all three control cases had only a diploid peak. Among the tumors, the DNA indices of the aneuploid peaks ranged from 1.1 to 2.2. The percentage of aneuploid cells ranged from 7 to 99, and no distinction was made between benign and malignant. Proliferation rates were estimated from the combined S-phase fractions (SPF). The mean SPF of the control group was 0.7% +/- 0.15% SD. The mean SPF of the benign tumors (1.1 +/- 0.82% SD) was significantly different from the malignant group (7.0 +/- 1.25% SD; range, 5.3 to 8.6%) P = 0.0095. Low SPF fractions always correlated with favorable outcome. Higher proliferation rates were generally associated with an aggressive course. Evaluation of proliferation rates may help predict the behavior of choroid plexus tumors, particularly when histological features are equivocal. Measurement of DNA ploidy does not appear to have a role in the evaluation of choroid plexus tumors.

Adolescent↗

PubMed2006

Metastatic atypical choroid plexus papilloma: a case report.

Choroid plexus papillomas (CPPs) are rare adult tumours and metastatic disease is even less common, more typically associated with choroid plexus carcinoma. We present the case of a 32-year-old patient with multiple metastases arising along the length of the neuraxis 3 years after resection of an atypical fourth ventricular CPP. Metastatic deposits were found from the mid-brain to the lumbar cistern and the patient underwent repeat excision of the fourth ventricular tumour, partial resection of a cervico-thoracic deposit and craniospinal radiotherapy. Possible explanations for the rarity of atypical CPP include unclear diagnostic criteria leading to under-representation in reported cases. We review the current literature on metastatic CPP and discuss the role of surgery and adjuvant therapy in relation to both typical and atypical disease.

Adult↗

PubMed1979

Tight junctions in choroid plexus papillomas.

Four cases of choroid plexus papilloma (CPP) obtained at the time of surgical excision were examined by electron microscopy and compared with normal choroid plexus (CP) of mouse and chick. In apical tight junctions fusion of the two outer leaflets of the adjacent cytoplasmic membrane was verified as in CP. This fact suggests that there is a blood-CSF barrier not only in CP but also in CPP.

Animals↗

PubMed1984

Immunohistochemical localization of Na+, K+-ATPase in the choroid plexus.

To determine if canine and rat choroid plexus Na+,K+-ATPase can be localized by immunoperoxidase staining after fixation and embedding, we prepared rabbit antiserum to purified canine kidney medulla Na+,K+-ATPase. When sodium dodecylsulfate polyacrylamide electrophoretic gels of purified canine kidney Na+,K+-ATPase and canine kidney microsomes were treated with antiserum followed by [125I]protein A and autoradiography, the canine microsomes and purified Na+,K+-ATPase showed a prominent radioactive band coincident with the alpha-, beta- and gamma-subunits of the purified canine kidney enzyme. When the rabbit immunoglobulin that was purified from the Na+,K+-ATPase antiserum through DEAE-cellulose ion exchange chromatography was used for immunoperoxidase staining of the choroid plexus fixed with Bouin's fixative, intense immunoreactive staining was present on the epithelial cells of both choroid plexuses but was not found in the tissue around the vessel. The staining was especially confined to apical surfaces of the epithelial cells. The same procedure was performed in the canine kidney, and immunostaining was obtained in the tubules where Baskin and Stahl described the enzyme localization. No staining was seen with pre-immune serum of the normal rabbit. We concluded that both the canine and rat choroid plexus are rich in Na+,K+-ATPase, which plays an important role in cerebrospinal fluid (CSF) secretion.

Animals↗

PubMed2001

Choroid plexus carcinoma in an adult.

Choroid plexus carcinomas are rare in adults. They can behave aggressively and their optimal management is uncertain. An adult patient with choroid plexus carcinoma who was treated with an incomplete surgical resection and postoperative radiotherapy is reported. Despite an identifiable local response to radiotherapy, disease progression resulted in death 4 years after presentation. This report reviews the current literature and discusses the management issues regarding this uncommon adult malignancy.

Adult↗

PubMed2002

Inward-rectifying anion channels are expressed in the epithelial cells of choroid plexus isolated from ClC-2 'knock-out' mice.

Choroid plexus epithelial cells express inward-rectifying anion channels which have a high HCO(3)(-) permeability. These channels are thought to have an important role in the secretion of cerebrospinal fluid. The possible relationship between these channels and the ClC-2 Cl(-) channel was investigated in the present study. RT-PCR, using specific ClC-2 primers, amplified a 238 bp fragment of mRNA from rat choroid plexus, which was 99 % identical to the 5' sequence of rat ClC-2. A 2005 bp clone was isolated from a rat choroid plexus cDNA library using a probe for ClC-2. The clone showed greater than 99 % identity with the sequence of rat ClC-2. Inward-rectifying anion channels were observed in whole-cell recordings of choroid plexus epithelial cells isolated from ClC-2 knock-out mice. The mean inward conductance was 19.6 plus minus 3.6 nS (n = 8) in controls (3 heterozygote animals), and 22.5 plus minus 3.1 nS (n = 10) in three knock-out animals. The relative permeability of the conductances to I(-) and Cl(-) (P(I) : P(Cl)) was determined. I(-) was more permeant than Cl(-) in both heterozygotes (P(I):P(Cl) = 4.0 +/- 0.9, n = 3) and knock-out animals (P(I) : P(Cl) = 4.1 +/- 1.4, n = 3). These results indicate that rat choroid plexus expresses the ClC-2 variant that was originally reported in other tissues. ClC-2 does not contribute significantly to inward-rectifying anion conductance in mouse choroid plexus, which must therefore express a novel inward-rectifying anion channel.

Algorithms↗

PubMed1995

Bone formation within a choroid plexus papilloma.

Bone formation within the choroid plexus papillomas is rare, with only 4 previous cases reported. We present a case of a 12-year-old boy who presented with papilledema, visual loss and hydrocephalus who was found to have a choroid plexus papilloma. Histological analysis of the tumor revealed foci of cancellous bone formation with hematopoietic cells within the marrow spaces. We review the proposed mechanisms for bone formation within neuroepithelial brain tumors.

Child↗

PubMed1986

Interaction between Trypanosoma brucei and the ependymal cell of the choroid plexus.

The fine structure of the normal choroid plexus of rats and mice and of those infected with Trypanosoma brucei was examined by transmission and scanning electron microscopy: extracellular trypomastigotes in the perivascular stroma predominate but the evidence presented suggests that they are derived both from stages in the blood and from others undergoing division within ependymal cells, a process which results in destruction of a large proportion of ependymal cells in the parts of choroid plexus affected. The choroid plexus maintains its integrity by regeneration of an outer layer of ependymal cells.

Animals↗

PubMed1986

Transport of prostaglandins and other eicosanoids by the choroid plexus: its characterization and physiological significance.

Choroid plexi from the lateral ventricles of rabbits, cats, and dogfish (Mustelus canis) were used to characterize the prostaglandin (PG) uptake process and to establish its kinetic parameters and substrate specificity. The apparent Kt for PGF2 alpha transport by the rabbit choroid plexus was 20 microM; the Jmax was 27 nmol g-1 min-1. The Ki of inhibition of PGF2 alpha transport by PGE2 was 20 microM; the Jmax of PGF2 alpha transport was unaltered by PGE2. A concentration of p-aminohippuric acid of up to 1 mM did not appreciably affect the Kt or the Jmax of PGF2 alpha transport. The rate of PGF2 alpha accumulation by rabbit choroid plexus was reduced by incubation at 4 degrees C, under anaerobic conditions, in the absence of sodium or in the presence of ouabain, probenecid, or bromcresol green. The choroid plexi of all three species also accumulated thromboxane B2, PGI2, and 6-keto-PGF1 alpha, suggesting that most, if not all, eicosanoids are substrates for this transport system. It is concluded that the choroid plexus transport system satisfies all the criteria of an active, energy-dependent transport system and that this system functions effectively at concentrations of eicosanoids present in the ventricular system under normal or pathological conditions. Hence, this transport system must make an important contribution to the pharmacokinetics of eicosanoids within the brain.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Fetal lateral ventricle choroid plexus cysts: the dilemma of amniocentesis.

Although lateral ventricle choroid plexus cysts in the second-trimester fetus have been considered a benign developmental phenomenon of no clinical significance, an association with trisomy 18 has been suggested. We designed a prospective study to determine whether karyotype analysis is indicated when such cysts are encountered on prenatal sonogram. During a 20-month period, 5400 low-risk pregnant women were examined sonographically in the second trimester to evaluate the prevalence of fetal lateral ventricle choroid plexus cysts and the incidence of ultrasonographic anomalies associated with such cysts in fetuses with trisomy 18 referred from cytogenetic laboratories. Thirty cases of fetal lateral ventricle choroid plexus cysts (0.6%) were detected during the study period; 28 newborns were normal and two had trisomy 18. One of the affected infants had other associated ultrasonographic abnormalities suggesting aneuploidy, whereas no detectable abnormalities could be found in the other. Three other pregnant women were referred to us from the cytogenetics services because fetal karyotype revealed trisomy 18; in all three cases lateral ventricle choroid plexus cysts and other sonographic abnormalities were observed. In total, we scanned five fetuses with trisomy 18, of which all had lateral ventricle choroid plexus cysts and four had associated detectable anomalies. We could not find any association between cyst size, number, or laterality and trisomy 18. In addition to the five cases of trisomy 18 described, we found 33 other fetuses reported with trisomy 18 in the second trimester; of this total, 25 (66%) had lateral ventricle choroid plexus cysts and 30% had no other detectable abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1996

NADPH-diaphorase histochemistry of rat choroid plexus blood vessels and epithelium.

Choroid plexus is the major source of cerebrospinal fluid. The hemodynamics and secretory function of this tissue are controlled by multiple endocrine and neural mechanisms. Nitric oxide (NO) has been demonstrated to play an important role in regulating choroidal blood flow. In the present study, performed on adult male Sprague-Dawley rats, we employed a NADPH-diaphorase (NADPH-d) histochemical method to localize nitrergic innervation of choroidal blood vessels. This approach was based on previous observations that NADPH-d colocalizes with NO synthase, a synthetic enzyme for NO, in the central and peripheral nervous systems. NADPH-d-positive nerve fibers were found to accompany both large arteries and veins and blood microvessels (possibly arterioles) located in choroidal stroma. NADPH-d reaction product was also localized to the vascular endothelial lining and choroidal epithelial cells. All the above sources of NO may play important roles in the regulation of secretory and hemodynamic functions of the choroid plexus.

Animals↗

PubMed1977

Neurologic complications of Hodgkin's disease. Choroid plexus involvement.

Involvement of the choroid plexus by lymphoma (Hodgkin) is a hitherto undescribed complication. We report herein the case of a 49-year-old man who developed, shortly before death, neurologic symptoms seemingly related to extensive involvement of choroid plexus and surrounding ventricular structures by lymphoma (Hodgkin's). There was also multifocal involvement of cranial nerves and spinal canal contents.

Cerebral Ventricle Neoplasms↗