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PubMed1987

Angioarchitecture of the human choroid.

The angioarchitecture of the human choroid was studied by corrosion vascular casts and scanning electron microscopy. The relationship of the large choroidal arteries and veins, medium-sized arteries and veins, precapillary arterioles and postcapillary venules, and the choriocapillaris is described. At the posterior pole, a lobular arrangement of the choriocapillaris is seen. At the equatorial area, the capillaries run a more direct course, joining the precapillary arterioles to the capillary venules in a spindle-shaped segment of the choroidal vasculature. At the periphery, the choroidal arterioles and venules take a parallel course, with the choriocapillaris joining the adjacent arterioles and venules at a right angle and appearing in a ladder pattern. The regional variation of the angioarchitecture of the human choroid provides supporting evidence for the unique regional characteristics of choroidal blood flow.

Aged↗
PubMed1988

Necrotic changes of choroidal melanocytes in sympathetic ophthalmia.

There are various theories as to the origin of epithelioid cells in the choroid with sympathetic ophthalmia. Some investigators propose a transformation of choroidal melanocytes as the origin, and others suggest a histiomonocytic derivation. One reason this controversy exists may be the relative lack of investigations into necrotic changes of choroidal melanocytes. The structural alterations in the choroidal melanocytes of an injured eye with sympathetic ophthalmia were studied, and the sequence of events involved in degeneration and necrotic changes were elucidated. The damaged melanocytes developed vacuolation, and the melanin granules were gathered into autophagosomes or had disappeared. The nuclei of the severely damaged melanocytes became pyknotic. Degenerated cell nuclei were phagocytized by macrophages. It is concluded that choroidal melanocytes may not transform into epithelioid cells and that they disappear from the choroid following degeneration.

Choroid↗
PubMed1995

Vessel formation by choroidal endothelial cells in vitro is modulated by retinal pigment epithelial cells.

OBJECTIVE: To elucidate the mechanism of bovine choroidal endothelial (BCE) cell angiogenesis and, in particular, the role of retinal pigment epithelial (RPE) cells by use of an in vitro coculture assay system. METHODS: The BCE cells were isolated from choroidal tissues and cultured. They were embedded in type I collagen gel and incubated. The gel-embedded BCE cells were then covered with a monolayer of RPE cells, pericytes, choroidal fibroblasts, or additional BCE cells on culture day 0 or day 14. The BCE cells in culture formed a meshwork of tubelike structures. The length of the tubelike structures (micrometers per field) was quantified by image analysis, as an indicator of angiogenesis. The effect of RPE cells on normal and growth-arrested BCE cell tube formation was evaluated in this assay system. The mechanism of RPE-induced angiogenesis was studied by parallel experiments with the use of neutralizing antibodies against specific growth factors (basic fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor beta). RESULTS: Ultrastructural analysis revealed that the tubelike structures had features typical of choroidal endothelial cells. Cocultures initiated on day 0 revealed that BCE cell angiogenesis was promoted by overlying RPE cells and, to a lesser extent, by pericytes, choroidal fibroblasts, and additional BCE cells when compared with BCE cells without covering cells. In cocultures initiated after BCE tube formation (day 14), there was inhibition of BCE angiogenesis by overlying RPE cells when compared with cultures without overlay or with an overlay of BCE cells. The RPE cells stimulated tube formation of growth-arrested BCE cells less effectively than did normal BCE cells. Neutralizing antibody for basic fibroblast growth factor and vascular endothelial growth factor, but not transforming growth factor beta, inhibited control and RPE-induced tube formation by BCE cells. CONCLUSIONS: Overlying RPE cells stimulate the formation of tubelike structures by choroidal endothelial cells more effectively than do fibroblasts or pericytes but inhibit BCE tube formation in older cultures. The effect involves endothelial proliferation and differentiation. The stimulatory effect of overlying RPE cells can be inhibited by neutralizing antibodies to vascular endothelial growth factor and basic fibroblast growth factor, which suggests that these growth factors play an important role in this phenomenon.

Animals↗
PubMed1995

Photodynamic therapy of experimental choroidal neovascularization using lipoprotein-delivered benzoporphyrin.

OBJECTIVE: To investigate photodynamic therapy of experimental choroidal neovascularization using benzoporphyrin derivative monoacid (Verteporfin). METHODS: Photodynamic therapy using benzoporphyrin derivative monoacid was investigated in cynomolgus monkeys. Following intravenous injection of benzoporphyrin derivative monoacid (1 to 2 mg/kg) complexed with low-density lipoprotein, the eyes were irradiated with 692-nm light at a fluence of 50 to 150 J/cm2 and irradiance of 150 to 600 mW/cm2. Choroidal neovascularization was documented before photodynamic therapy and closure was demonstrated by fundus photography, fluorescein angiography, and light and electron microscopic examination. RESULTS: Following photodynamic therapy, vessels within choroidal neovascularization were occluded, and there was damage to the choroidal neovascularization endothelium and the subjacent choriocapillaris. Damage to the retinal pigment epithelium and photoreceptors was also observed. CONCLUSION: Photodynamic therapy with lipoprotein-delivered benzoporphyrin derivative monoacid was effective in this animal model of choroidal neovascularization and may be a promising, potentially selective, therapy for choroidal neovascularization.

Animals↗
PubMed1998

Ependymal and choroidal cells in culture: characterization and functional differentiation.

During the past 10 years, our teams developed long-term primary cultures of ependymal cells derived from ventricular walls of telencephalon and hypothalamus or choroidal cells (modified ependymal cells) derived from plexuses dissected out of fetal or newborn mouse or rat brains. Cultures were established in serum-supplemented or chemically defined media after seeding on serum-, fibronectin-, or collagen-laminin-coated plastic dishes or semipermeable inserts. To identify and characterize cell types growing in our cultures, we used morphological features provided by phase contrast, scanning, and transmission electron microscopy. We used antibodies against intermediate filament proteins (vimentin, glial fibrillary acidic protein, cytokeratin, desmin, neurofilament proteins), actin, myosin, ciliary rootlets, laminin, and fibronectin in single or double immunostaining, and monoclonal antibodies against epitopes of ependymal or endothelial cells, to recognize ventricular wall cell types with immunological criteria. Ciliated or nonciliated ependymal cells in telencephalic cultures, tanycytes and ciliated and nonciliated ependymal cells in hypothalamic cultures always exceeded 75% of the cultured cells under the conditions used. These cells were characterized by their cell shape and epithelial organization, by their apical differentiations observed by scanning and transmission electron microscopy, and by specific markers (e.g., glial fibrillary acidic protein, ciliary rootlet proteins, DARPP 32) detected by immunofluorescence. All these cultured ependymal cell types remarkably resembled in vivo ependymocytes in terms of molecular markers and ultrastructural features. Choroidal cells were also maintained for several weeks in culture, and abundantly expressed markers were detected in both choroidal tissue and culture (Na+-K+-dependent ATPase, DARPP 32, G proteins, ANP receptors). In this review, the culture models we developed (defined in terms of biological material, media, substrates, duration, and subculturing) are also compared with those developed by other investigators during the last 10 years. Focusing on morphological and functional approaches, we have shown that these culture models were suitable to investigate and provide new insights on (1) the gap junctional communication of ependymal, choroidal, and astroglial cells in long-term primary cultures by freeze-fracture or dye transfer of Lucifer Yellow CH after intracellular microinjection; (2) some ionic channels; (3) the hormone receptors to tri-iodothyronine or atrial natriuretic peptides; (4) the regulatory effect of tri-iodothyronine on glutamine synthetase expression; (5) the endocytosis and transcytosis of proteins; and (6) the morphogenetic effects of galactosyl-ceramide. We also discuss new insights provided by recent results reported on in vitro ependymal and choroidal expressions of neuropeptide-processing enzymes and neurosecretory proteins or choroidal expression of transferrin regulated through serotoninergic activation.

Animals↗
PubMed2001

Cell death in the choroid plexus following transient forebrain global ischemia in the rat.

Following a complete disruption of blood flow to the brain, cerebral ischemia, a specific neuronal population, namely the CA1 pyramidal neurons in the hippocampus, will die a delayed type of cell death. This is often referred to as "delayed neuronal death" (DND). It is not known why it takes around 48 hours for these cells to die. It is very often speculated that events, intrinsic to the CA1 neurons, regulate their demise, whereas it is less often considered that extrinsic mechanisms also could play an important role for the development of DND. We discovered that in addition to the CA1 pyramidal neurons, cells in the choroid plexus were TUNEL (terminaldeoxynucleotidyl-mediated biotin-dUTP nick-end labeling)-positive following transient forebrain global ischemia. The time course and the number of TUNEL-positive cells were determined. A dramatic increase in the number of TUNEL-positive cells in the choroid plexus was seen at 18, 24, and at 36 hours of recovery, but not at 48 hours of recovery following 15 minutes of transient forebrain global ischemia. No TUNEL-positive cells were seen at 24 hours of recovery in the CA1 region. The cell death in the choroid plexus thus preceded the occurrence of cell death in the CA1 region. Massive cell death in the choroid plexus will inevitably lead to a leaky blood-CSF barrier, which in turn will allow substances to enter the ventricular system and from there reach the brain parenchyma. We, therefore, conclude that choroid plexus cell death may adversely affect the outcome of CA1 pyramidal neurons following transient forebrain global ischemia, through, e.g., a disruption of the blood-cerebro spinal fluid barrier. Alternatively, the choroid plexus may produce factors, which can affect the outcome of neurons.

Animals↗
PubMed2001

Brain drug delivery, drug metabolism, and multidrug resistance at the choroid plexus.

The choroid plexuses (CPs) have the capability to modulate drug delivery to the cerebrospinal fluid (CSF) and to participate in the overall cerebral biodisposition of drugs. The specific morphological properties of the choroidal epithelium and the existence of a CSF pathway for drug distribution to different targets in the central nervous system suggest that the CP-CSF route is more significant than previously thought for brain drug delivery. In contrast to its role in CSF penetration of drugs, CP is also involved in brain protection in that it has the capacity to clear the CSF from numerous potentially harmful CSF-borne exogenous and endogenous organic compounds into the blood. Furthermore, CP harbors a large panel of drug-metabolizing enzymes as well as transport proteins of the multidrug resistance phenotype, which modulate the cerebral bioavailability of drugs and toxins. The use of an in vitro model of the choroidal epithelium suitable for drug transport studies has allowed the demonstration of the choroidal epithelium acting as an effective metabolic blood-CSF barrier toward some xenobiotics, and that a vectorial, blood-facing efflux of conjugated metabolites occurs at the choroidal epithelium. This efflux involves a specific transporter with characteristics similar to those of the multidrug resistance associated protein (MRP) family members. Indeed, at least one member, MRP1, is largely expressed at the CP epithelium, and localizes at the basolateral membrane. These metabolic and transport features of the choroidal epithelium point out the CP as a major detoxification site within the brain.

ATP-Binding Cassette Transporters↗
PubMed1988

Vascularization of the telencephalic choroid plexus of a ganoid fish [Acipenser ruthenus (L.)].

The vascularization of the telencephalic choroid plexus of the sterlet Acipenser ruthenus, a ganoid fish, was examined by vascular corrosion casting and by light and transmission electron microscopy. The arterial supply is from the dorsal mesencephalic artery via: 1) the ventral choroidal arteries (left and right); 2) the dorsal choroidal arteries (left and right); 3) the caudal choroidal arteries (left and right); 4) the ventral arteries of the dorsal sac; and, from the olfactory arteries, via 5) the rostral choroidal arteries. The venous drainage is mainly through a single main choroidal vein that can take various courses either directly to the anterior cardinal vein or via the middle cerebral vein to the anterior cardinal vein. To a lesser extent, the plexus is drained via the lateral telencephalic veins and the ventral vein of the dorsal sac to the middle cerebral vein. By angioarchitecture and form, the plexus can be subdivided into five distinct parts: the surface network, the median folds, the large lateral folds, the small lateral folds, and the area common to the bottom of the dorsal sac and the telencephalic plexus. Diameters of terminal vessels as measured from vascular corrosion casts and from paraplast, semithin, and ultrathin sections were never less than 10 micron. It is suggested that the different areas in one plexus may have different functions with respect to secretion and absorption of cerebrospinal fluid.

Animals↗
PubMed2003

Structural characteristics and barrier properties of the choroid plexuses in developing brain of the opossum (Monodelphis Domestica).

The structural and functional development of the choroid plexuses, the site of the blood-cerebrospinal fluid (CSF) barrier, in an opossum (Monodelphis domestica) was studied. Marsupial species are extremely immature at birth compared with more conventional eutherian species. Choroid plexus tissue of each brain ventricle, from early stages of development, was collected for light and electron microscopy. During development, the choroidal epithelium changes from a pseudostratified to a cuboidal layer. Individual epithelial cells appear to go through a similar maturation process even though the timing is different between and within each plexus. The ultrastructural changes during development in the choroidal epithelial cells consist of an increase in the number of mitochondria and microvilli, and changes in structure of endoplasmic reticulum. There are also changes in the core of plexuses with age. In contrast, the structure of the tight junctions between epithelial cells does not appear to change with maturation. In addition, the route of penetration for lipid insoluble molecules from blood to CSF across the choroid plexuses was examined using a small biotin-dextran. This showed that the tight junctions already form a functional barrier in early development by preventing the paracellular movement of the tracer. Intracellular staining shows that there may be a transcellular route for these molecules through the epithelial cells from blood to CSF. Apart from lacking a glycogen-rich stage, cellular changes in the developing opossum plexus seem to be similar to those in other species, demonstrating that this is a good model for studies of mammalian choroid plexus development.

Animals↗
PubMed1988

Transport of digoxin into brain microvessels and choroid plexuses isolated from guinea pig.

To characterize the efflux system of digoxin, a cardiac glycoside, from the brain to the blood through the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, the accumulation of digoxin by the brain microvessel or the choroid plexus isolated from guinea pig brain was investigated. The accumulation of digoxin by the brain microvessel has a saturable component (Km = 0.163 microM, Vmax = 0.142 nmol/mL of tissue/min), with a nonsaturable component [Kd = 0.203 cell-to-medium (C:M) ratio/min] that was decreased by hypothermia (Q10 = 2.9), sulfhydryl reagent, and quinidine, but not by a metabolic inhibitor [2,4-dinitrophenol (DNP)]. It was concentration- and Na+-dependent. The accumulation of digoxin by the choroid plexus was also saturable (Km = 1.9 microM, Vmax = 3.8 nmol/mL of tissue/min), and was decreased by hypothermia (Q10 = 4.4), sulfhydryl reagents, ouabain, and quinidine, but not by metabolic inhibitors (DNP, KCN); it was also concentration- and Na+-dependent. The binding of digoxin to the homogenate of choroid plexus was one-tenth of digoxin accumulation by the intact choroid plexus, suggesting that digoxin is transported into the cells and bound to the cytosol fraction. The value of (Vmax/Km + Kd) multiplied by the total tissue weight of the microvessel per guinea pig is approximately 10-fold that of Vmax/Km multiplied by the tissue weight of the choroid plexus, although (Vmax/Km + Kd) per milliliter of the microvessel is half the Vmax/Km value of the choroid plexus. These findings suggest that digoxin can be excreted from both the brain and the cerebrospinal fluid to blood by a carrier-mediated diffusion system which is inhibited by quinidine, and that a main route of digoxin efflux from the brain to the blood is not through the blood-CSF barrier, but through the blood-brain barrier.

Animals↗
PubMed1995

Distinct adhesive properties of ciliary and choroid neurons from the avian ciliary ganglion.

The avian ciliary ganglion (CG) contains two populations of neurons: ciliary neurons, which innervate striated muscle, and choroid neurons, which innervate vascular smooth muscle. We used cell size (ciliary cells are larger) and somatostatin immunoreactivity (which is restricted to choroid cells) as markers to compare the adhesive properties of these two neuronal types. Similar numbers of freshly dissociated embryonic chick ciliary and choroid neurons adhered to laminin (laminin 1) and polylysine, consistent with the fact that each population comprises about half of the ganglionic neurons. In contrast, severalfold more ciliary neurons than choroid neurons adhered to a recombinant fragment of a synapsespecific basal lamina protein, s-laminin/laminin beta 2. Moreover, severalfold more ciliary neurons than choroid neurons adhered to a plastic surface when assayed by the method of Needels et al. in serum-free medium. Adhesion to s-laminin and plastic appears to be mediated by different cell surface components, as adhesion to recombinant s-laminin is inhibited by the tripeptide, LRE, and by Ca2+ ions, but not by heparin, whereas adhesion to plastic is LRE and Ca2+ insensitive but heparin sensitive. Both adhesive differences are apparent at embryonic day 8, soon after the ciliary and choroid neurons have begun to form synapses. Thus, two sets of neurons in the CG that send axons through different nerves and innervate different targets also show distinct adhesive behaviors.

Animals↗
PubMed1981

The fate of plasma protein which escapes from blood vessels of the choroid plexus of the rat--an electron microscope study.

Fenestrated blood vessels in the rat choroid plexus are permeable to dye-labelled proteins, HRP and ferritin. Most leakage appears to be via fenestrae but some additional escape of marker appears to take place through transient and reversible openings in the junctions between endothelial cells. After they have escaped into the choroidal stroma markers are prevented from entering the CSF by tight junctions between the epithelial cells which cover the choroid plexus, but how they are removed from the extravascular space is not known. Electron microscope study of rats who have been given multiple intravenous injections of ferritin shows that extravascular ferritin is take up both by connective tissue cells in the choroidal stroma and by choroidal epithelial cells. The findings suggest that the ingested protein is subsequently broken down within lysosomal vacuoles in the cytoplasm of these cells. Such intracellular digestion may be the major means of controlling the protein content of the extravascular spaces of the choroid plexus.

Animals↗
PubMed1994

Isolated choroid plexus cysts--the need for routine offer of karyotyping.

The management of isolated fetal choroid plexus cysts remains controversial. We have prospectively studied 15,565 pregnancies at two large obstetric units for the presence of choroid plexus cysts. In all cases where cysts were present at 19 weeks' gestation or greater, and were multiple, bilateral or solitary and greater than 5 mm maximum diameter, women were offered amniocentesis or placental biopsy, irrespective of the presence or absence of other abnormalities. Choroid plexus cysts were present in 152 (0.98 per cent) of cases. Four cases (2.6 per cent) of autosomal trisomy (three of trisomy 18, one of trisomy 21) were detected on prenatal karyotyping. In all cases, choroid plexus cysts were the only detectable prenatal anomaly. This study and a review of other large studies do not support the view that isolated choroid plexus cysts are a benign variant, the risk of trisomy being 1 in 82. Until further evidence is available, we recommend that cases of isolated fetal choroid plexus cysts at 19 weeks' gestation or greater should be offered prenatal karyotyping.

Amniocentesis↗
PubMed1998

Effects of timolol and betaxolol on choroidal blood flow in the rabbit.

This study evaluated the effects of the topical beta1-adrenergic antagonist betaxolol and the non-selective beta-adrenergic antagonist timolol on the choroidal pressure-flow relationship. Pentobarbital-anesthetized rabbits were instrumented with hydraulic occluders on the aorta and inferior vena cava to control MAP, an ear artery cannula to measure mean arterial pressure (MAP), and two vitreous cannulas to control and measure intraocular pressure (IOP). Choroidal blood flow was measured by laser Doppler flowmetry with the fiber-optic probe tip positioned over the posterior pole. Choroidal pressure-flow curves were obtained before and 30 min after topical application of 0.1 ml of betaxolol (Betoptic, 0.5%, n=10), timolol (Timoptic, 0.5%, n=10) or saline (n=8) by varying the MAP without controlling the IOP and by raising IOP while holding the MAP constant at 70 mmHg. The IOP was significantly reduced by betaxolol and timolol but not by saline. MAP was also slightly, but significantly, reduced after betaxolol but not after timolol or saline. However, the systemic hypotensive response to isoproterenol (8 microgram/kg, i.v.) was blunted after betaxolol and timolol indicating appreciable systemic absorption of both drugs. Timolol, but not betaxolol or saline, caused a significant, small increase in baseline choroidal vascular resistance. Timolol also attenuated the IOP response to MAP; however, none of the treatments had a significant effect on the choroidal pressure-flow relationship. We conclude that both drugs reach the systemic circulation after topical application, but neither betaxolol nor timolol alter the choroidal response to acute changes in perfusion pressure.

Adrenergic beta-Antagonists↗
PubMed1999

Modulation of choroidal autoregulation in the rabbit.

Previous studies show that the choroid can maintain its blood flow despite changes in perfusion pressure, behaviour possibly mediated by an autoregulatory mechanism. However, the choroid's rich autonomic innervation suggests possible neural involvement in the response. To evaluate the potential neural contribution, choroidal blood flow was measured by laser Doppler flowmetry over a wide range of perfusion pressure before and after ganglionic blockade in anaesthetized rabbits. Although an upward shift in the pressure-flow (P-F) curve was anticipated due to loss of adrenergic tone, ganglionic blockade shifted the P-F curve downward, prompting a search for a neural vasodilator to explain the response. Cholinergic blockade with atropine failed to alter the P-F curve suggesting little parasympathetic involvement. By contrast, inhibition of nitric oxide (NO) synthase with nitro-L-arginine methyl ester (L-NAME) caused a dramatic downward shift in the P-F curve, suggesting the nitridergic nerves as the source of vasodilatory tone. However, the downward shift in the P-F curve with L-NAME was greater than seen with ganglionic blockade, indicating that endothelial NO rather than neural dilator tone predominates. Moreover, calcium channel blockade after L-NAME reversed the downward shift in the P-F curve suggesting that choroidal vascular tone is modulated by an interaction between NO and an unknown vasoconstrictor. Neither hexamethonium, losartan or a vasopressin antagonist given after L-NAME reversed the downward shift in the P-F curve, ruling out a neural vasoconstrictor, angiotensin II and vasopressin as the source of constrictor tone. Phentolamine given after L-NAME caused a small but significant reversal of the downward shift in the P-F curve, suggesting a minor adrenergic contribution. By contrast, the non-selective endothelin antagonist, A-182086, given after L-NAME significantly attenuated the choroidal constriction. These results indicate that an unknown neural dilator and locally produced NO and endothelin exert competing influences on the inherent reactivity of the choroidal resistance vessels as they respond to changes in perfusion pressure, and that this local regulation is likely modulated by extrinsic neurohumoral factors that are relatively quiet in the anesthetized rabbit.

Animals↗
PubMed2002

Immunohistochemical staining and morphometric analysis of the monkey choroidal vasculature.

The purpose of this study was to develop a method for staining non-human primate choroidal blood vessels for combined whole mount and histologic analysis. Ten monkey eyes were used in this study. Diabetic and non-diabetic aged rhesus monkeys ranging in age from 16 to 31 years were killed and eyes were obtained immediately after death. Anterior segments were removed and retinas dissected from the posterior eyecup. Eyecups were soaked in 0.1% EDTA for 1hr to remove the retinal pigment epithelium (RPE). The whole choroids were dissected from the sclera, fixed in 2% paraformaldehyde and processed for immunohistochemical demonstration of perlecan, a heparan sulfate proteoglycan, using a streptavidin alkaline phosphatase technique. The alkaline phosphatase reaction product was developed using Histomark Red. Following immunohistochemical staining, choroids were incubated for the enzyme histochemical demonstration of non-specific esterase to label granulocytes. Anti-perlecan was localized to the endothelial cells of viable choroidal blood vessels and provided excellent staining of the choriocapillaris in all regions. Morphometric measurements of choriocapillaris were made in wet preparations using digitized images and image analysis software. The staining was absent in degenerated choroidal capillaries (lacking endothelial cells), thus allowing for sites of pathology to be identified and analysed. The reaction product was retained within the tissue throughout the flat-embedding process and allowed for precise site-specific identification of angiopathic lesions en bloc during sectioning. This technique provides a method of staining monkey choroidal blood vessels in situ and allows for identification and analysis of pathologic changes associated with aging or diseases.

Animals↗
PubMed1996

Chronic lead exposure alters transthyretin concentration in rat cerebrospinal fluid: the role of the choroid plexus.

The choroid plexus, which is responsible for the maintenance of the biochemical milieu of the cerebrospinal fluid (CSF), avidly sequesters Pb. In order to test the hypothesis that chronic Pb exposure may impair choroid plexus function, male weanling Sprague-Dawley rats were exposed to Pb in drinking water at doses of 0, 50, or 250 micrograms Pb/ml (as Pb acetate) for 30, 60, or 90 days. The function of the choroid plexus was assessed as reflected by CSF concentrations of transthyretin (TTR, a major CSF protein manufactured by brain choroid plexus) and CSF essential metal ions (Ca2+, Mg2+, K+, and Na+). TTR concentrations were determined by radioimmunoassay using a monospecific rabbit anti-rat TTR polyclonal antibody, and CSF metal ions analyzed by flame atomic absorption spectrophotometry. Two-way ANOVA of CSF TTR concentrations revealed highly significant dose (p < 0.0001), time (p < 0.0223), and dose-by-time effects (p < 0.0379). Moreover, the percentage of reduction of CSF TTR was directly correlated with Pb concentrations in the choroid plexus (r = 0.703, p < 0.05). Pb exposure significantly increased CSF concentrations of Mg2+, but did not markedly altered CSF concentrations of Ca2+, K+, and Na+. Histopathologic examination under the light microscope did not show distinct alterations of plexus structure in Pb-treated rats. Since TTR is responsible for transport of thyroid hormones to the developing brain, we postulate that the depression of choroid plexus TTR production (and/or secretion) by Pb may impair brain development in young animals by depriving the CNS of thyroid hormones.

Administration, Oral↗
PubMed1998

Lead exposure promotes translocation of protein kinase C activities in rat choroid plexus in vitro, but not in vivo.

Lead (Pb) exposure reportedly modulates PKC activity in brain endothelial preparations, which may underlie Pb-induced damage at the blood-brain barrier. Our previous work indicates that Pb accumulates in the choroid plexus and causes dysfunction of this blood-cerebrospinal fluid (CSF) barrier. The present studies were undertaken to test the hypothesis that Pb in the choroid plexus may alter PKC activity and thus affect the functions of the blood-CSF barrier. When choroidal epithelial cells in a primary culture were exposed to Pb (10 microM in culture medium), the membrane-bound PKC activity increased by 5.2-fold, while the cytosolic PKC activities decreased, an indication of the induction of PKC translocation by Pb. The effect of Pb on cellular PKC was concentration dependent in the range of 0.1-10 microM. We further evaluated PKC activity of the choroid plexus in rats chronically exposed to Pb in the drinking water (control, 50 or 250 micrograms Pb/ml) for 30, 60, or 90 days. Two-way analysis of variance revealed a significant age-related decline of PKC activities in both cytosol and membrane of the choroid plexus. However, Pb treatment did not alter plexus PKC activities. In addition, we found that short-term, acute Pb exposure in rats did not significantly change PKC activities nor did it affect the expression of PKC isoenzymes in the choroid plexus. Our results suggest that Pb exposure may promote the translocation of PKC from cytosol to membrane in rat blood-CSF barrier in vitro, but not in vivo.

Animals↗