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PubMed1993

Expression of neuropeptide processing enzymes and neurosecretory proteins in ependyma and choroid plexus epithelium.

Recent studies suggest that brain ependyma and choroid plexus produce neuropeptide processing enzymes. To facilitate the understanding of these cells and their ability to produce biologically active peptides, we developed cultures of defined cell type. Ependymal cells were characterized by morphological criteria, and choroid plexus epithelial cell lines were characterized by the presence of the mRNA for IGF-II and transthyretin, a thyroxine binding protein produced in liver and choroid plexus. The ependymal cells and the choroid plexus epithelial cell lines were then examined for the presence of mRNAs for various neuropeptide processing enzymes. Northern blot analysis revealed high levels of furin, carboxypeptidase E, and peptidyl glycine alpha-amidating monooxygenase mRNAs, with levels in ependymal cells comparable to those in brain or pituitary. Carboxypeptidase E activity was detected in medium from cultured ependymal cells; this activity was identified as carboxypeptidase E based on the acidic pH optimum and sensitivity to various inhibitors. The mRNAs for other neuropeptide processing enzymes, such as prohormone convertases 1 and 2, were not detected on Northern blots of RNA from ependyma or choroid plexus epithelium. Since ependyma and choroid plexus epithelium express a subset of processing enzymes, we suggest that these cells have the capacity to produce biologically active peptides. Initial screening by reverse transcriptase-polymerase chain reaction assays has demonstrated the presence of mRNA for the neurosecretory proteins chromogranin B and secretogranin II in both ependyma and choroid plexus epithelium.

Animals↗

PubMed1975

Choroid plexus isografts in rats.

Choroid plexuses from adult rats were grafted to the kidneys of other rats of the same inbred strain. Almost all the grafts survived and exhibited a multiloculated pattern of choroidal papillae. Mild but progressive enlargement of the locules was probably caused by secretion of cerebrospinal fluid. Cyclophosphamide, a drug which damages the normally situated plexus, had similar but milder effects on the plexus implants. Isografts should prove useful for other studies of choroid plexus structure and function.

Animals↗

PubMed1991

Serotonergic effects on carbonic anhydrase activity in the choroid plexus.

The carbonic anhydrase (CA) activities in the choroid plexus of dogs were investigated by electron microscopy, and the effects of 5-hydroxytryptophan (5-HTP) on them were examined to elucidate the participation of serotonin in the production of cerebrospinal fluid. The reaction products yielded by the method employed proved to be CA activity by elimination tests using acetazolamide (Diamox). Following administration of 5-HTP, the CA activities fell to 43.3% of the control value, that is, approximately 56% of the CA activities in the choroid plexus were affected by serotonin. When tetrabenazine (TBZ) was administered, the CA activities in the choroid plexus decreased to 22.4% of the control value. These results suggest that the CA activity in the choroid plexus is remarkably suppressed when nervous control of the choroid plexus is disturbed by the administration of a monoamine denervator such as TBZ. The present data indicate that the serotonergic inhibitory effect on the CA activity in the choroid plexus may be less predominant than that of TBZ and acetazolamide.

5-Hydroxytryptophan↗

PubMed1987

Choroid plexus tumors in children: immunohistochemical and scanning-electron-microscopic features.

The 30 choroid plexus tumors recorded in a large pediatric tumor registry were reviewed. The 22 choroid plexus papillomas and 8 choroid plexus carcinomas represented 2.1% of all brain tumors in the registry. The patients (19 boys, 11 girls) were aged 3 months to 12 years (mean: 2 years 9 months). All tumors and four samples of normal choroid plexus were examined with conventional histology, 9 tumors were examined with electron microscopy and 24 using immunohistochemical techniques with antisera against glial fibrillary acidic protein, S-100 protein, epidermal cytokeratin, internal organ cytokeratin and carcinoembryonic antigen. Seven of the tumors (1 carcinoma and 6 papillomas) had some positive cells with antiserum against glial fibrillary acidic protein. Twenty-seven of the tumors (90%) and all normal choroid plexus samples were positive with antiserum to S-100 protein. Some tumor cells from both types of tumor and the normal choroid plexus reacted positively with internal organ cytokeratin antiserum, but all tissue samples were nonreactive with epidermal cytokeratin antiserum. Ultrastructurally, both papillomas and carcinomas displayed cytoplasmic intermediate filaments. Transmission and/or scanning electron microscopy revealed cilia in all choroid plexus papillomas. Frequently, the cilia had an abnormal arrangement, varying from 5 + 0 to 8 + 1. This study demonstrates that tumor cells of choroid plexus origin are characterized by the presence of S-100 protein and internal organ cytokeratin antiserum. Cilia, either normal or abnormal, are consistently identified in papillomas but rarely and with difficulty in carcinomas. Carcinoembryonic antigen is seen in choroid plexus carcinomas but not papillomas.

Adolescent↗

PubMed1992

Gene expression and receptor binding of insulin-like growth factor-II in pig choroid plexus epithelial cells.

To elucidate the function of insulin-like growth factor-II (IGF-II) in the choroid plexus, the gene expression and receptor binding of IGF-II were studied in isolated epithelial cells from the porcine choroid plexus. The choroid plexus expressed multiple IGF-II transcripts of 1.2, 1.6, 2.4, and 4.4 kb, at levels higher than those found in porcine liver and kidney. These data suggest that IGF-II is synthesized by the choroid plexus. Choroid plexus epithelial cells contained high levels of IGF-I receptors on the cell surface whereas very low levels of receptor binding were found for 125I-IGF-II and 125I-insulin. Solubilization of epithelial cells showed that a large proportion of the IGF-I receptors were present in the detergent-insoluble fraction whereas IGF-II receptors and insulin receptors were concentrated in the detergent-soluble fraction. These results suggest that IGF-I receptors are located in clathrin-coated pits of the plasma membrane whereas IGF-II receptors and insulin receptors are present in endosomal vesicles. The tyrosine kinase activity of the IGF-I receptor beta-subunit was stimulated by IGF-I, IGF-II, and insulin, in order of potency, suggesting that these peptides exert a regulatory function in the choroid plexus epithelium. In conclusion, we propose that the IGF-I receptor tyrosine kinase on the surface of the epithelial cells in the pig choroid plexus mediates effects of IGF-I and IGF-II, whereas IGF-II receptors are down-regulated due to the synthesis and secretion of IGF-II in these cells.

Affinity Labels↗

PubMedDate not supplied

Choroid plexus hemorrhage in premature neonates: recognition by sonography.

In 34 consecutive infants admitted to the neonatal intensive care unit with birth weight of less than 1,500 g, 80 cranial real-time sonograms were obtained to determine the incidence of choroid plexus hemorrhage. Choroid plexus hemorrhage was diagnosed only in the absence of germinal matrix hemorrhage. Diagnostic criteria included choroid plexus nodularity, enlargement (greater than 12 mm in anteroposterior diameter), or asymmetry between right and left (greater than 5 mm). Ipsilateral intraventricular clots or occipital horn dilatation supported the diagnosis of choroid plexus hemorrhage in most cases. Choroid plexus hemorrhage appeared to be the sole bleeding site in 10 (59%) of the 17 patients with intracranial hemorrhage. Hemorrhage in the region of the caudate nucleus was seen in the other seven cases (41%). Ventricular dilatation and/or intraventricular hemorrhage accompanied nine (90%) of the 10 cases of choroid plexus hemorrhage. This study suggests that in very low-birth-weight premature neonates, the choroid plexus may be a more frequent site of intracranial hemorrhage than previously believed.

Cerebral Hemorrhage↗

PubMedDate not supplied

Current management of choroid plexus carcinoma in children.

Eleven children with choroid plexus carcinoma are reviewed with respect to presentation, radiographic diagnosis, treatment and pathologic histology. These cases accumulated over a 33-year period and represent 39% of all of our choroid plexus tumors (n = 28). Characteristically, choroid plexus carcinomas are associated with a poor prognosis for long-term survival. Unfortunately, efforts at total resection are hindered in part by the extreme vascularity of the tumor which itself may be of considerable volume. We have recently treated four children who had biopsy or minimal resection of their tumor after which adjuvant chemotherapy was given. Chemotherapy is not curative but it does cause a reduction in tumor volume and, more importantly, has tended to reduce the tumor vascularity. This allows for a second stage operation which is more safely performed and typically allows for more complete tumor removal. At this point, our length of follow-up is insufficient to conclude if total removal in this manner significantly increases survival but it would seem that consistent gross total removal may be an initial step toward better overall management and prognosis in this tumor type.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1975

[Electron microscopic study of choroid plexus in experimentally induced hydrocephalic dog (author's transl)].

Choroid plexus in experimentally induced hydrocephalic dogs according to the Wisniewski's method was examined by an electron microscope. Epithelial cell of the choroid plexus appeared in various deformation and formed a marked dilatation of extracellular spaces between apposed two cell membranes and at the basal interdigitation. Dilatation of the extracellular space was more pronounced at the stromal side of the epithelial layer. This finding might be due to anatomical specificities of apposed epithelial cell membranes and not only indicate a disturbance of the CSF secretion. According to the dilatation of extracellular space, apposed two epithelial cell membranes separated each other, however, at sites of intercellular junctions, adjacent cell membranes remained closely apposed. The dilated extracellular space at the basal site continued to the dilated intercellular space, while, no continuity was recognized between the dilated intercellular space and ventricular lumen. These extracellular speces appeared low electron density and showed little specific structure. No particular change was recognized in organelles in the epithelial cell, except increased pinocytotic vesicles in number. Stroma of the choroid plexus appeared edematous, that was, electron density was low and a few cellular and stromal elements were found. Capillary vessels showed almost normal structure. In hydrocephalic dogs also in normal one, Lanthanum infused into lateral ventricle precipitated on the surface of microvilli of choroid plexus epithelial cell. The Lanthanum, entered through ventricular end of intercellular space, was blocked to penetrate beyond the intercellular junction (zonula occludens) and any bit of the tracer was not found in the dilated extracellular space. The tracer was found neither in epithelial cell nor in stroma. These findings of tracer-study may indicate that the CSF absorption through the choroid plexus is not increased in chronic hydrocephalus. Consequently, the ultrastructural changes of the choroid plexus in chronic hydrocephalus, that is, enlarged extracellualr space, increased pinocytotic vesicles and edematous stroma, are thought to suggest a disturbance of CSF secretion from the choroid plexus.

Animals↗

PubMed2002

Some observations of the structure of the choroid plexus and its cysts.

The structure of the choroid plexus was studied in five normal human embryos, three normal fetuses and three fetuses with choroid plexus cysts. These were detected by ultrasound and the fetuses were karyotypically normal. The choroid plexus appears in the lateral cerebral ventricles at the seventh developmental week. The early structure is lobulated with vessels running in the mesenchymal stroma and forming capillary nets under the single-layered ependymal epithelium. This embryonal structure is converted into the fetal type during the ninth developmental week as the embryonal capillary net is replaced by elongated loops of wavy capillaries that lie under regular longitudinal epithelial folds. The choroid plexus cysts exhibited accumulation of fluid within distended mesenchymal stroma and did not show the wavy folds on this surface, which was smooth. Within this connective tissue of the cyst wall were distended angiomatous interconnecting thin-walled capillaries. Therefore, filled cavities were not lined by any epithelium. We suggest that fetal choroid plexuses cysts (at least in many cases) are in fact pseudocysts exhibiting angiomatous patterns of capillaries in their walls.

Capillaries↗

PubMed1989

Cyst of the fetal choroid plexus: a normal variant?

Cysts of the choroid plexus have been identified ultrasonographically in second-trimester fetuses and usually have regressed by 24 weeks' gestation. Choroid plexus cysts have been linked with trisomy 18, and this possible association has prompted a review of our experience. Choroid plexus cysts were seen ultrasonographically in 38 consecutive fetuses between 15 and 28 weeks' gestation. Of these, 30 underwent repeat ultrasonograms after 24 weeks' gestation and showed complete resolution of the cysts. In 10 of the 38 fetuses, amniocentesis yielded normal karyotypes. A total of 36 patients were delivered of normal neonates at term. One patient was delivered of a normal neonate prematurely, at 34 weeks' gestation with a good outcome. Another fetus was delivered at 36 weeks' gestation because of late onset of nonimmune hydrops, which resolved without sequelae. No association between trisomy 18 and choroid plexus cysts was identified in this series.

Choroid Plexus↗

PubMed1989

The subcellular distribution of transferrin in rat choroid plexus studied with immunogold labelling of ultracryosections.

Choroid plexus epithelium from third ventricle choroid plexus of 2-3-week-old rats was examined for transferrin-like immunoreactivity. In 5 microns paraffin sections most epithelial cells exhibited a pronounced immunoperoxidase staining for transferrin. The ultrastructure of the epithelium in question was examined by conventional electron microscopy. Immunolabelling of ultracryosections with IgG-gold, protein-A gold or protein-A gold-antiprotein-A protein-A gold showed an intense labelling of the basal extracellular space. The lateral intercellular space and the luminal surface showed a more variable labelling; no labelling of the tight junction zone was seen. Intracellularly a distinct labelling of the 'uptake and disposal pathway' (the endosomal-lysosomal system) was observed, but also the synthetic machinery (rough endoplasmic reticulum, stacked Golgi membranes) showed a characteristic labelling. Thus it seems likely that both uptake and synthesis of transferrin occur in choroid plexus epithelial cells.

Animals↗

PubMed1976

Antidiuretic peptide in mammalian choroid plexus.

Lyophilized bovine, porcine, and human choroid plexuses contain .02-.09 U of antidiuretic activity per milligram. The antidiuretic factor in bovine choroid plexus was concentrated 100 times by extraction with acetic acid, fractional precipitation with acetone and ethyl ether, gel filtration, and paper chromatography. Resulting choroid plexus fraction IIgammaB2 was eluted from Sephadex G-25 in position corresponding to molecular weight between 750 and 3,500; its antidiuretic activity was destroyed by trypsin, performic acid, and thioglycollic acid, but was not affected by leucine aminopeptidase, carboxypeptidase A or B, or cyanogen bromide. HgammaB2 possesses antidiuretic, pressor, and oxytocic potencies (measured in anesthetized-hydrated rat, anesthetized rat, and isolated rat uterus, respectively) of 1.9, 0.5, and 0.1 U/mg, respectively.

Aminopeptidases↗

PubMed2004

Neurite outgrowth from hippocampal neurons is promoted by choroid plexus ependymal cells in vitro.

Choroid plexus ependymal cells (CPECs) were known to promote axonal growth when choroid plexus is grafted into the adult rat spinal cord. The present study was carried out to examine whether CPECs promote axonal outgrowth from neurons derived from the CNS in vitro. Hippocampal neurons were cocultured on CPEC monolayers. After 24 h, neurite extension was evaluated using various parameters in comparison with cultures grown on poly-L-lysine (PLL)-coated plates and cocultures grown on astrocyte monolayers. The primary neurite length and total neurite length were longest in the cocultures with CPECs. The number of primary neurites and the number of branches were larger in the cultures with CPECs than in the cultures on PLL-coated plates, but almost the same as in the cocultures with astrocytes. Next, we examined whether the neurite extension-promoting effect occurring within 24 h is due primarily to contact with the CPECs or to factors secreted by CPECs into the culture medium. The CPEC monolayers were killed by ethanol fixation, and neurons cultured on them. The neurons extended long neurites with elaborate branching, as in the case of cocultures grown on living CPECs. On the other hand, CPEC-conditioned medium exhibited less promoting effect on neurite outgrowth from hippocampal neurons. These results indicate that CPECs have a capacity to promote neurite outgrowth from CNS neurons in vitro , and that surface plasma membrane-bound components of CPECs strongly contribute to the enhancement of neurite outgrowth in the present coculture system.

Animals↗

PubMed2006

Prognostic implications of atypical histologic features in choroid plexus papilloma.

The prognostic significance of atypical histologic features in choroid plexus tumors remains uncertain. Therefore, a series of 164 choroid plexus tumors was evaluated for the presence of atypical histologic features, including mitotic activity, increased cellularity, nuclear pleomorphism, blurring of papillary growth pattern, and necrosis. The impact of histopathologic and clinical features on the probability of recurrence and survival was investigated. Twenty-four tumors displaying frank signs of malignancy were diagnosed as choroid plexus carcinoma according to World Health Organization criteria. Of 124 choroid plexus papillomas that had not received adjuvant treatment, 46 tumors (37%) displayed at least one atypical feature, including increased cellularity (n = 25 [20%]), mitotic activity (> or =2 mitoses per 10 high-power fields; n = 19 [15%]), nuclear pleomorphism (n = 16 [13%]), solid growth (n = 15 [12%]), and necrosis (n = 5 [4%]). Only one tumor-related death, but 10 recurrences, were observed on a mean observation time of 58 months. On univariate analysis, incomplete surgical resection (p = 0.03) and mitotic activity (p < 0.001) were the only clinicopathologic factors associated with recurrence. Using a multivariate model, an independent effect of mitotic activity on the probability of recurrence could be confirmed (p = 0.001). Because mitotic activity is the sole atypical histologic feature independently associated with recurrence, we propose to define atypical choroid plexus papilloma by mitotic activity (> or =2 mitoses per 10 high-power fields) corresponding to World Health Organization grade II, thus adjoining other intermediate tumor entities associated with increased mitotic activity such as atypical meningioma. Close follow up of patients harboring atypical choroid plexus papillomas may be warranted.

Adult↗

PubMedDate not supplied

Tubular adenoma of choroid plexus: a case report.

A case of choroid plexus neoplasm histologically composed of tubular structures lined by a layer of cuboidal epithelium is reported. The neoplasm was located in the fourth ventricle of a 26-year-old man. The intense positivity for antisera anti-vimentin, anti-cytokeratin, anti-EMA and anti-S100 protein exhibited by these cells was consistent with choroid plexus origin. The patient is alive and in good health 5 years after surgery. The lesion represents a benign choroid plexus neoplasm not previously reported. The name "tubular adenoma of choroid plexus" is suggested for this variant.

Adenoma↗

PubMed1994

Effect of endogenous vasopressin on blood flow to choroid plexus during hypoxia and intracranial hypertension.

Exogenous vasopressin decreases blood flow to the choroid plexus and production of cerebrospinal fluid. Some studies indicate that hypoxia and increases in intracranial pressure (ICP) produce increases in circulating vasopressin. We examined the hypothesis that endogenous release of vasopressin decreases blood flow to the choroid plexus during hypoxia and increased ICP. Blood flow to the choroid plexus was measured in anesthetized rabbits using microspheres. Hypoxia increased cerebral blood flow more than twofold but had little effect on blood flow to the choroid plexus. In contrast, hypoxia produced a marked increase in blood flow to the choroid plexus in the presence of a vasopressin V1-antagonist, [d(CH2)5Tyr(Me)]AVP. During intracranial hypertension, blood flow to the choroid plexus decreased from 409 +/- 42 to 295 +/- 25 ml.min-1 x 100 g-1 (means +/- SE; P < 0.05 vs. control) when ICP was increased from 1 to 40 mmHg. The vasopressin antagonist inhibited the decrease in blood flow to the choroid plexus in response to increased ICP. Thus release of vasopressin during hypoxia and increased ICP have a constrictor effect on blood vessels of the choroid plexus. Plasma levels of vasopressin increased minimally during hypoxia and increased ICP, which suggests that sources of vasopressin other than plasma affect blood vessels of the choroid plexus. We propose that endogenous vasopressin may play a protective role during hypoxia and intracranial hypertension by a negative feedback mechanism to reduce blood flow to the choroid plexus.

Animals↗

PubMed2001

Human choroid plexus growth factors: What are the implications for CSF dynamics in Alzheimer's disease?

The choroid plexus plays a key role in supporting neuronal function by secreting cerebrospinal fluid (CSF) and may be involved in the regulation of various soluble factors. Because the choroid plexus is involved in growth factor secretion as well as CSF dynamics, it is important to understand how growth factors in CSF interact with the brain parenchyma as well as with cells in direct contact with the flowing CSF, i.e., choroid plexus and arachnoid villi. While the existence of growth factors in the choroid plexus has been documented in several animal models, the presence and distribution of growth factors in the human choroid plexus has not been extensively examined. This study describes the general distribution and possible functions of a number of key proteins in the human choroid plexus and arachnoid villi, including basic fibroblast growth factor, FGF receptor, and vascular endothelial growth factor. FGF and VEGF could both be readily demonstrated in choroid plexus epithelial cells. The presence of FGF and VEGF within the choroid plexus was also confirmed by ELISA analysis. Since Alzheimer's disease (AD) is known to be associated with a number of growth factor abnormalities, we examined the choroid plexus and arachnoid villi from AD patients. Immunohistochemical studies revealed the presence of FGF and VEGF within the AD choroid plexus and an increased density of FGFr in both the choroid plexus and the arachnoid villi of AD patients. No qualitative changes in the distribution of FGF and VEGF were observed in the AD choroid plexus. The appearance of FGFr in AD arachnoid was associated with robust amyloid and vimentin immunoreactivity. These findings confirm the presence of FGF and VEGF within the normal and AD choroid plexus and suggest that the alteration of growth factors and their receptors may contribute to the pathogenesis of the hydrocephalus ex vacuo that is characteristically seen in AD.

Alzheimer Disease↗

PubMed2004

Choroid plexus papilloma associated with developmental delay.

Choroid plexus papillomas are rare, benign tumors of neuroectodermal origin usually observed in the lateral ventricles of children. The usual presenting signs of choroid plexus papillomas are related to hydrocephalus and increased intracranial pressure. A child presented to us with clinical features of delayed milestones, which was later diagnosed as a case of choroid plexus papilloma with hydrocephalus. He underwent complete excision of the tumour with gradual recovery of milestones.

Developmental Disabilities↗