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PubMed1985

Response of a recurrent choroid plexus tumor to combination chemotherapy.

Choroid Plexus tumors are rare. Surgery and biopsy is diagnostic, and radiotherapy has been used as the treatment of choice for choroid plexus carcinoma (CPC) and recurrent choroid plexus papilloma (CPP). We report the first case of CPP responding to combination chemotherapy consisting of cisplatin, bleomycin and vinblastine (CBV). This chemotherapy regimen should be considered for future trials in patients with choroid plexus tumors and recurrence after surgery and/or radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach.

To identify specific markers for the diagnosis of choroid plexus tumors, gene expression profiles of choroid plexus epithelial cells (n = 8) and ependymal cells (n = 6) microdissected from human autopsy brains as well as choroid plexus papilloma tissue were investigated using DNA microarrays. Protein expression of genes overexpressed in choroid plexus was evaluated in normal choroid plexus, choroid plexus papilloma, choroid plexus carcinoma, other primary brain tumors, and cerebral metastases. Forty-six genes found to be overexpressed in normal choroid plexus epithelial cells were also present in choroid plexus papilloma. Among those, 11 were further analyzed by immunohistochemistry. Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases. Similarly, stanniocalcin-1 stained normal choroid plexus (32 of 35), choroid plexus papilloma (16 of 18), and choroid plexus carcinoma (3 of 5), whereas staining was seen in only 2 of 100 other primary brain tumors and cerebral metastases. Transthyretin stained choroid plexus (33 of 35), choroid plexus papilloma (14 of 18), and plexus carcinoma (2 of 5), but its specificity was significantly lower. Antibodies directed against coagulation factor V, glutathione peroxidase 3, pigment epithelium derived factor, serotonin receptor 5-HTR2C, lumican, fibulin-1, plastin-1, and cytokeratin 18 revealed varying degrees of specificity and sensitivity. Our data suggest that antibodies directed against Kir7.1 and stanniocalcin-1 might serve as sensitive and specific diagnostic markers for choroid plexus tumors.

Adult↗

PubMed1989

Developmental patterns of gene expression of secreted proteins in brain and choroid plexus.

The proteins secreted by the choroid plexus throughout rat brain development were analyzed by two-dimensional polyacrylamide gel electrophoresis following biosynthetic labeling of choroid plexus pieces with [14C]leucine in vitro. Approximately 20 major protein species were resolved which, with the exception of transferrin, transthyretin, and alpha 2-macroglobulin, appear to be unrelated to proteins found in high concentrations in plasma. Several patterns of developmental regulation were observed. At least two of the proteins were synthesized and secreted at high levels only by fetal choroid plexus, whereas the secretion of several other proteins including transferrin and proteins comigrating with cystatin C and alpha 2-macroglobulin increased only after birth. The levels of mRNA coding for transferrin, ceruloplasmin, cystatin C, alpha 2-macroglobulin, beta 2-microglobulin, and transthyretin were measured in the brain during development by dot hybridization and northern gel analysis. No mRNA was detected coding for the proteins alpha-fetoprotein, alpha 1-antitrypsin, haptoglobin, and thiostatin in the brain at any stage. For those proteins, which are produced in other parts of the brain as well as by the choroid plexus, the changes in their corresponding mRNA levels measured in whole brain paralleled the changes in their secretion by the choroid plexus. The results presented in this paper show that the choroid plexus is active in protein secretion at all stages studied. The changing pattern of protein secretion by the choroid plexus, combined with its early development compared with other tissues in the brain, suggests that it is active in providing the appropriate extracellular environment for the growth and differentiation of the brain.

Aging↗

PubMedDate not supplied

Pathological and immunohistochemical studies of choroid plexus carcinoma of the dog.

Choroid plexus carcinomas in four dogs (three male, one female) aged small middle 2.5 to 10 years, were examined by light microscopy and immunohistochemistry. The dogs showed progressive neurological signs including ataxia, seizures, vestibular disease and cranial nerve deficits, lasting for several months in some cases. Primary tumours were localized in the lateral (one case), third (one case), and fourth (two cases) ventricles. Hydrocephalus was evident at post-mortem examination in one case. In two cases the neoplastic cells closely resembled the structure of normal choroid plexus, with a distinct papillary pattern, composed of well-differentiated columnar epithelium. In the other two cases, cellular pleomorphism, nuclear atypia, increased mitotic activity and necrosis were observed. In all cases, dissemination of neoplastic cell clusters was detected within the subarachnoid space or the ventricular cavity. Immunohistochemical examination showed a multifocal labelling pattern for pankeratin and cytokeratin AE1 and diffuse vimentin positivity in poorly differentiated tumours. Well-differentiated choroid plexus carcinomas showed multifocal immunoreactivity for cytokeratin AE3, multifocal to diffuse immunoreactivity for vimentin and occasional positivity for carcinoembryonic antigen. Epithelial membrane antigen, Ber EP4 and S-100 were negative in all cases. Glial fibrillary acidic protein labelling occurred only in a single, poorly differentiated tumour. Occasional reactions for proliferating cell nuclear antigen and MIB-1 were seen in two cases. It was concluded that at least two morphological and possibly phenotypic subtypes (well-differentiated and anaplastic) of choroid plexus carcinoma of the dog could be identified.

Animals↗

PubMed1995

Immunohistochemical localization of the glucose transporter GLUT1 in choroid plexus papillomas.

Normal chroid plexus tissue and five choroid plexus papillomas were examined with antibody specific for the glucose transporter GLUT1, one isoform of facilitated-diffusion glucose transporters, using the avidin-biotin-peroxidase complex (ABC) technique. GLUT1 in normal choroid plexus was localized at the basolateral plasma membrane of almost all epithelial cells. In three of five tumors, GLUT1 immunoreactivity was observed. A positive reaction was demonstrated at the plasma membrane of tumor cells. The number of GLUT1-positive cells was, however, much smaller than that of the normal choroid plexus. Our results suggest that GLUT1 expression in the choroid plexus is restrained during the course of transformation and that choroid plexus papilloma is composed of various differentiation tumor cells.

Adolescent↗

PubMed1978

Sympathetic nervous control of cerebrospinal fluid production from the choroid plexus.

The rabbit choroid plexus, responsible for the bulk production of cerebrospinal fluid, is well supplied by sympathetic nerves emanating in the superior cervical ganglia. Electrical stimulation of these nerves markedly reduces production of cerebrospinal fluid, measured by [14C] inulin dilution during ventricular perfusion, whereas sympathetic denervation enhances the rate of formation.

Adrenergic Fibers↗

PubMed1976

Ultrastructural evidence for CSF production by a choroid plexus papilloma.

A choroid plexus papilloma (CPP) removed from a child with communicating hydrocephalus was studied with the electron microscope. In addition to the usual organelles, the neoplastic epithelial cells contained polypoid microvilli, cilia, coated pinocytotic vesicles, and apical tight junctions. The basal surfaces were consistently juxtaposed to large capillaries lined by fenestrated endothelium. The fine structural details of the tumor were essentially the same as those of normal CP and thus appeared ideally suited for an active secretory function. Two additional features in this tumor were tubular bodies in the endothelium and well developed pericytes. The present findings provide strong evidence for cerebrospinal fluid production by CPP, a phenomenon that has long been suggested by clinical observation.

Brain Neoplasms↗

PubMed2005

Direct and indirect roles of CNS dorsal midline cells in choroid plexus epithelia formation.

Choroid plexus (CP) produces the cerebrospinal fluid (CSF) of the central nervous system (CNS), but little is known about the mechanisms underlying development of this important tissue. CP forms in the hindbrain (4th ventricle), diencephalon (3rd ventricle) and dorsomedial telencephalon bilaterally (lateral ventricles). All of these sites lie at or near the embryonic dorsal midline (DM), which acts as a CNS patterning center. We therefore examined DM-CP relationships using normal and Gdf7 (Bmp12) transgenic embryos to fate map or ablate DM cells. These studies revealed a Gdf7 fate map that includes most CP epithelial (CPe) cells of the hindbrain and diencephalon. In the telencephalon, Gdf7 cell lineages were found in the small anterior domain of telencephalic CPe (tCPe), but its large posterior domain was devoid of these lineages. Anterior and posterior tCPe domains, which arise within a contiguous field separate from diencephalic CPe, also exhibited different patterns of apoptosis. Despite lacking Gdf7 cell lineages, the posterior tCPe domain failed to form after ablating Gdf7-expressing DM cells at neural tube stages. The tCPe loss was associated with abrogation of high-level bone morphogenetic protein (Bmp) signaling, which is known to be required for tCPe induction. Taken together, these studies demonstrate intimate DM-CPe relationships throughout the CNS and highlight two distinct tCPe domains, including a posterior domain whose genesis depends on DM cells in a non-cell-autonomous fashion.

Animals↗

PubMed1990

A marker for primary choroid plexus neoplasms.

Primary choroid plexus (CP) tumors are rare neoplasms that present in childhood or, less frequently, in adult life. The majority are benign and amenable to complete surgical excision, but occasionally more invasive variants are encountered. Although generally pathologically distinct, occasionally primary CP neoplasms may be difficult to distinguish from metastatic papillary carcinomas or papillary ependymomas. Conventional cytologic markers are not sufficiently specific to permit accurate diagnosis of primary CP tumors. The authors have reported that the CP is the unique site of synthesis within the brain of transthyretin (TTR, prealbumin), a transport protein for thyroxine and retinol. They therefore investigated the utility of TTR as a biochemical marker for CP tumors. They detected intense immunoreactivity for TTR at high dilutions of primary antiserum in the neoplastic epithelium of all of nine primary CP tumors (six papillomas and three carcinomas), but not in eight cellular or three papillary intracerebral ependymomas, meningiomas, oligodendrogliomas, astrocytomas, primary extracerebral papillary carcinomas (three thyroid, two breast) or five of six cerebral metastases from systemic papillary carcinomas. In one case of cerebral metastasis from papillary thyroid carcinoma, rare isolated immunoreactive cells were observed. Faint staining of the stromal-ependymal junction was seen in myxopapillary ependymomas of the filum terminale, which were otherwise nonreactive. By in situ hybridization, TTR mRNA was abundant in neoplastic CP epithelium, confirming local TTR synthesis. The authors conclude that TTR is synthesized by neoplastic CP epithelium and is an excellent marker for primary CP neoplasms.

Adolescent↗

PubMed1985

Thymidine transport and metabolism in choroid plexus: effect of diazepam and thiopental.

Choroid plexus contains an active transport (influx) and a facilitated diffusion (efflux) system for nucleosides. The ability of diazepam and thiopental to inhibit active transport or facilitated diffusion of thymidine in choroid plexus was measured in vitro under various conditions. When isolated rabbit choroid plexuses were incubated in artificial cerebrospinal fluid containing 1 microM [3H] thymidine for 10 min at 37 degrees C under 95% O2-5% CO2, diazepam (10 microM) and thiopental (500 microM) doubled the tissue-to-medium ratios of [3H] thymidine from 8 to 15 to 16. These results were not due to metabolism or intracellular binding but rather to inhibition of [3H] thymidine efflux from choroid plexus. Diazepam, unlike thiopental, inhibited [3H] thymidine efflux in a concentration-dependent manner. When isolated choroid plexuses were incubated in artificial cerebrospinal fluid containing low concentrations of [3H] thymidine (6 nM) to allow intracellular conversion of [3H] thymidine into [3H] thymidine phosphates and [3H] DNA, both diazepam (10 microM) and thiopental (500 microM) altered [3H] thymidine accumulation and metabolism consistent with inhibition of facilitated diffusion but not active transport of thymidine. These studies provide evidence that, at toxic but not therapeutic concentrations, diazepam and thiopental alter facilitated nucleoside transport in the choroid plexus.

Animals↗

PubMed1995

Mechanisms of nucleobase transport in rabbit choroid plexus. Evidence for a Na(+)-dependent nucleobase transporter with broad substrate selectivity.

The overall goal of this study was to determine the mechanisms by which nucleobases are transported in the choroid plexus. Choroid plexus tissue slices were obtained from the lateral ventricles of rabbit brains and depleted of ATP with 2,4-dinitrophenol. In the presence of an initial inwardly directed Na+ gradient, hypoxanthine accumulated in the tissue slices against a concentration gradient. Na(+)-stimulated hypoxanthine uptake was saturable with a Km of 31.1 +/- 9.71 microM and a Vmax of 2.69 +/- 0.941 nmol/g/s (mean +/- S.E.). Na(+)-stimulated hypoxanthine uptake was inhibited by (100) microM naturally occurring purine and pyrimidine nucleobases (adenine, cytosine, guanine, hypoxanthine, thymine, uracil, and xanthine) as well as by the nucleoside analog, dideoxyadenosine. The stoichiometric coupling ratio between Na+ and hypoxanthine was 1.7:1. The data demonstrate the presence of a novel Na(+)-dependent nucleobase transporter in the choroid plexus, which is distinct from the previously described Na(+)-nucleoside transporter in choroid plexus and from Na(+)-dependent nucleobase transporters in other tissues in terms of its kinetics, substrate selectivity, and Na(+)-nucleobase stoichiometry. This transporter may play a role in the targeting of both salvageable nucleobases and therapeutic nucleoside analogs to the central nervous system.

2,4-Dinitrophenol↗

PubMed1980

Choroid plexus blood flow in the sheep.

Choroid plexus blood flow was measured in 29 adult female sheep using the radioactive microsphere technique. Basal blood flow, response to change in arterial carbon dioxide tension, and response to change in mean arterial blood pressure were determined. The results were compared to cerebral cortical blood flow values in the same sheep. Mean choroid plexus blood flow was 601 ml/100 g/min under basal conditions. Choroid plexus blood flow fell 31% with hypocarbia, a reduction comparable to that seen in cortex. With hypercarbia choroid plexus blood flow rose only 27% whereas cortical blood flow increased by 199%. Unlike cortical blood flow, choroid plexus blood flow fell significantly with pharmacogenic hypertension. The latter finding may reflect the absence of a blood-brain barrier in choroid plexus.

Animals↗

PubMed1989

A prospective study of the incidence and significance of fetal choroid plexus cysts.

Cysts of the choroid plexus of the lateral ventricle can be detected in the fetus during routine scanning at 16-18 weeks' gestation with an approximate incident of one in every 120 pregnancies. It is likely that in a high percentage of cases cysts are bilateral and that their recent discovery is mainly due to improvements in imaging technology. Although the great majority of cases resolve and do not result in any morbidity, five cases of trisomy 18 and one case of trisomy 21 associated with fetal choroid plexus cysts have been reported. In this prospective study, choroid plexus cysts were detected in 42 fetuses, resulting in 40 normal infants and 2 cases of trisomy 18. It is concluded that there may be a relationship between fetal choroid plexus cysts and trisomy 18. In order to obtain a more precise and accurate result, a multi-centre prospective study is being organized.

Brain Diseases↗

PubMed1996

Choroid plexus papilloma of the cerebellopontine angle.

Choroid plexus papillomas are rare tumors, representing less than 1% of all intracranial neoplasms in our review of the English literature. Derived from the neuroepithelial cells of the choroid plexus, these tumors recapitulate the structure of the normal choroid plexus, often demonstrating a well-developed papillary architecture. This tumor most commonly affects children and typically arises in the lateral ventricles. Before 1992, 26 cases have been reported arising in the cerebellopontine angle. We describe an example of choroid plexus papilloma of the cerebellopontine angle that was initially diagnosed as metastatic papillary carcinoma. A metastatic disease workup revealed a right thyroid lobe nodule. Fine needle aspiration biopsy of this nodule yielded a few atypical cells, but no evidence of papillary carcinoma. We performed additional laboratory investigations to rule out the possibility of a primary papillary carcinoma of the thyroid gland and to make a definitive diagnosis of a choroid plexus papilloma. This article reviews choroid plexus papilloma of the cerebellopontine angle and demonstrates the use of immunohistochemistry to differentiate this benign primary neoplasm from well-differentiated metastatic papillary carcinoma.

Adult↗

PubMed1986

Serotonin 5-HT1C receptors are expressed at high density on choroid plexus tumors from transgenic mice.

Choroid plexus tumors develop spontaneously in adult transgenic mice carrying integrated copies of SV40 early region genes. In this communication, we report that these tumors exhibit the highest density of serotonin receptors (6600 fmol/mg protein) found in any tissue. 125I-LSD binding to choroid plexus tumors displays a pharmacological profile that matches the properties of 5-HT1C receptors in normal choroid plexus tissue. Autoradiographic localization of 125I-LSD binding in brain sections from transgenic mice shows high levels of labelling in the tumors, in correlation with immunohistochemical staining for SV40 large T antigen expression. Choroid plexus tumors from these transgenic mice provide an excellent model system for the study of serotonin 5-HT1C receptors.

Animals↗

PubMed2004

Infarction of the choroid plexus.

Infarction of the choroid plexus may result from ischemia in the distribution of the medial posterior choroidal artery. Diffusion-weighted imaging may depict this unusual stroke syndrome. The clinical and radiologic aspects of this rare condition are discussed taking into consideration the anatomy and pathophysiology of the choroid plexus.

Calcinosis↗

PubMed1998

Dichotomous development of the organic anion transport protein in liver and choroid plexus.

Both adult liver and choroid plexus express the organic anion transport protein (oatp1) and transport [35S]bromosulfophthalein (BSP). Studies of the developing rat liver reveal that oatp1 mRNA and protein do not begin to be expressed until 15 days postnatal and are at adult levels by 30 days. Uptake of [35S]BSP follows the same time course. In contrast, neonatal rat choroid plexus expresses oatp1 mRNA and protein. When quantified on a weight basis, the uptake of [35S]BSP in choroid plexus is lower in the adult than at earlier stages of development. Although fluorescence confocal microscopy of adult rat choroid plexus shows that oatp is localized to the apical surface, facing the cerebrospinal fluid, this method reveals an intracellular localization of oatp1 in the neonate. Approximately 12 wk are required for the appearance of the adult pattern of distribution. Changes in the localization and activity of oatp1 during development could play an important role in the pathobiology of maturation of the liver and the central nervous system.

Aging↗

PubMed2001

Claudin-1, claudin-2 and claudin-11 are present in tight junctions of choroid plexus epithelium of the mouse.

The choroid plexus epithelium forms the blood-cerebrospinal fluid (CSF) barrier and is responsible for the secretion of the CSF from the blood. The morphological correlate of the blood-CSF barrier are the tight junctions of choroid plexus epithelium. By freeze-fracture electron microscopy it has been demonstrated that choroid plexus epithelial tight junctions form parallel strands resembling those of Sertoli cells building the blood-testis barrier and those of the myelin sheaths of oligodendrocytes. As the oligodendrocyte specific protein/claudin-11 has been shown to be the central mediator of parallel-array tight junctions in Sertoli cells and myelin sheaths in mice, we asked whether claudin-11 is present in the tight junctions of choroid plexus epithelial cells of the mouse. Here, we present the first direct evidence that claudin-11 besides claudin-1 and -2, occludin and the zonula occludens protein ZO-1 is present in choroid plexus epithelial tight junctions. During inflammation in the central nervous system such as experimental autoimmune encephalomyelitis, the molecular composition of choroid plexus epithelial tight junctions does not change considerably. Their unique molecular composition, with claudin-11 accompanied by claudin-1 and claudin-2 points to a unique regulatory mechanism of the blood-CSF-barrier function.

Animals↗