Cotransport of sodium and chloride by the adult mammalian choroid plexus

1990 ◽  
Vol 258 (2) ◽  
pp. C211-C216 ◽  
Author(s):  
C. E. Johanson ◽  
S. M. Sweeney ◽  
J. T. Parmelee ◽  
M. H. Epstein
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Drug Effects ◽  
Disulfonic Acid ◽  
Base Line ◽  
Sprague Dawley ◽  
Disulfonic Stilbene ◽  
Fluid Formation ◽  
Vitro Analysis

Cerebrospinal fluid formation stems primarily from the transport of Na and Cl in choroid plexus (CP). To characterize properties and modulation of choroidal transporters, we tested diuretics and other agents for ability to alter ion transport in vitro. Adult Sprague-Dawley rats were the source of CPs preincubated with drug for 20 min and then transferred to cerebrospinal fluid (CSF) medium containing 22Na or 36Cl with [3H]mannitol (extracellular correction). Complete base-line curves were established for cellular uptake of Na and Cl at 37 degrees C. The half-maximal uptake occurred at 12 s, so it was used to assess drug effects on rate of transport (nmol Na or Cl/mg CP). Bumetanide (10(-5) and 10(-4) M) decreased uptake of Na and Cl with maximal inhibition (up to 45%) at 10(-5) M. Another cotransport inhibitor, furosemide (10(-4) M), reduced transport of Na by 25% and Cl by 33%. However, acetazolamide (10(-4) M) and atriopeptin III (10(-7) M) significantly lowered uptake of Na (but not Cl), suggesting effect(s) other than on cotransport. The disulfonic stilbene 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 10(-4) M), known to inhibit Cl-HCO3 exchange, substantially reduced the transport of 36Cl. Bumetanide plus DIDS (both 10(-4) M) caused additive inhibition of 90% of Cl uptake, which provides strong evidence for the existence of both cotransport and antiport Cl carriers. Overall, this in vitro analysis, uncomplicated by variables of blood flow and neural tone, indicates the presence in rat CP of the cotransport of Na and Cl in addition to the established Na-H and Cl-HCO3 exchangers.

Benzodiazepine receptors and cerebrospinal fluid formation

1990 ◽  
Vol 72 (5) ◽  
pp. 759-762 ◽  
Author(s):  
Gregg L. Williams ◽  
Michael Pollay ◽  
Thomas Seale ◽  
Brent Hisey ◽  
P. Alex Roberts
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Binding Sites ◽  
Benzodiazepine Receptors ◽  
Secretory Activity ◽  
Assay Method ◽  
Content Type ◽  
High Affinity ◽  
Fluid Formation

✓ There is autoradiographic evidence that peripheral-type benzodiazepine ligands bind with high affinity to the membranes of choroid plexus tissue. In this study, the binding of a 4′-chloro analog of diazepam (Ro 5-4864) to rabbit choroid plexus and cerebral cortex was accomplished utilizing an in vitro radioactive assay method. A kinetic analysis of this binding revealed a relatively high affinity of this ligand (KD) for peripheral binding sites in plexus tissue (KD = 16.1 nM/mg protein). There was a 4.6-fold greater density of binding sites (total receptor density (Bmax) = 2.3 pmol/mg) in choroidal membrane as compared to cortical tissue (Bmax = 0.5 pmol/mg). In 40 rabbits in which a ventricular perfusion system was used, the rate of cerebrospinal fluid (CSF) formation was observed to decrease some 48% in the presence of 10−4 M Ro 5-4864, although some inhibition of secretory activity was still noted at a CSF concentration of 10−8 M. The choroid plexus tissue levels of adenosine 3′,5′cyclic monophosphate (cAMP) and adenosine triphosphatase (ATPase) were not affected by 10−4 M Ro 5-4864. The results of this study support the notion that the specific benzodiazepine peripheral binding sites in choroid plexus serve to modulate CSF formation. The mechanism of action is poorly understood but does not involve the transport ATPase system or the second messenger cAMP.

Maturational differences in acetazolamide-altered pH and HCO3 of choroid plexus, cerebrospinal fluid, and brain

1992 ◽  
Vol 262 (5) ◽  
pp. R909-R914 ◽  
Author(s):  
C. E. Johanson ◽  
Z. Parandoosh ◽  
M. L. Dyas
Keyword(s):  
Cerebrospinal Fluid ◽  
Cerebral Cortex ◽  
Carbonic Anhydrase ◽  
Choroid Plexus ◽  
Intracellular Ph ◽  
Ph Regulation ◽  
Secretory Process ◽  
Sprague Dawley ◽  
Infant Rats ◽  
Fluid Formation

The carbonic anhydrase inhibitor acetazolamide is useful for analyzing ion transport, pH regulation, and fluid formation in developing central nervous system. We used the 14C-labeled dimethadione technique to measure alterations in steady-state pH, and to estimate the HCO3 concentration [HCO3], in choroid plexus (CP), cerebrospinal fluid (CSF), and cerebral cortex of 1- and 3-wk-old Sprague-Dawley rats treated with acetazolamide or probenecid. These drugs can suppress transport of HCO3 and other anions in some cells, consequently altering intracellular pH. In 1-wk-old infant rats whose CSF secretory process is incompletely developed, 1 h of acetazolamide treatment did not significantly change CP intracellular pH or [HCO3]. However, in 3-wk-old rats, in which the ability of CP to secrete ions and fluids is almost fully developed, acetazolamide caused marked increases in CP cell intracellular pH and [HCO3]. In contrast, acetazolamide-induced alkalinization was not observed in CSF or cerebral cortex of the 1- and 3-wk-old animals. The other test agent, probenecid (an inhibitor of anion transport but not of carbonic anhydrase), did not alter the pH of any region at any age investigated. Overall, the results are interpreted in light of developmental changes in carbonic anhydrase and previous findings from kinetic analyses of ion-translocating systems in CP. Acetazolamide may interfere with a CP apical membrane HCO3 extrusion mechanism not fully operational in infant rats.

Relationship between arterial and cisternal CSF oxygen tension in rabbits

1979 ◽  
Vol 236 (3) ◽  
pp. F220-F225
Author(s):  
L. Jankowska ◽  
P. Grieb
Keyword(s):  
Cerebrospinal Fluid ◽  
Linear Regression ◽  
Choroid Plexus ◽  
Oxygen Tension ◽  
Linear Regression Equation ◽  
Mechanically Ventilated ◽  
Fluid Formation ◽  
And Function ◽  
Ionic Exchanges ◽  
Arterial Po2

Oxygen tension was measured in samples of blood and cisternal cerebrospinal fluid taken from anesthetized, paralyzed, and mechanically ventilated rabbits at various levels of arterial PO2. Cerebrospinal fluid oxygen tension (CSF PO2) was correlated with arterial PO2 (linear regression equation PCSFO2 = 0.2472 Pao2 + 42.34). During hypoxia CSF PO2 was higher than arterial PO2 in most experiments. These data can be attributed to the Bohr effect, which would increase the PO2 of the blood in choroid plexus capillaries as a result of its acidification. The acidification was suggested by Maren (Am. J. Physiol. 222: 885-889, 1972) to be a part of the ionic exchanges involved in cerebrospinal fluid formation. Such a mechanism may be of importance for supporting choroid plexus metabolism and function during hypoxia. This mechanism is most clearly seen in the rabbit.

Myo-inositol transport in the central nervous system

1975 ◽  
Vol 228 (5) ◽  
pp. 1510-1518 ◽  
Author(s):  
R Spector ◽  
AV Lorenzo
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Choroid Plexus ◽  
Intraventricular Injection ◽  
Affinity Constant ◽  
Rapid Injection ◽  
The Central Nervous System

Free myo-inositol (inositol) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the cerebrospinal fluid was measured in rabbits. In vivo, inositol transport from blood into choroid plexus, CSF, and brain was saturable with an apparent affinity constant (K-t) of approximately 0.1 mM. The relative turnover of free inositol in choroid plexus (16 percent/h) was higher than in CSF 4percent/h) and brain (0.3percent/h) when meausred by tissue penetration of tracer [3-H]-labeled inositol injected into blood. However, the passage of tracer inositol was not greater than the passage of mannitol into brain when measured 15 s after a rapid injection of inositol and mannitol into the left common carotid artery. From the CSF, the clearance of inositol relative to inulin was saturable after the intraventricular injection of various concentrations of inositol and inulin. Moreover, a portion of the inositol cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [3-H-labeled myo-inositol against a concentration gradient by a specific, active, saturable process with a K-t of 0.2 mM inositol. These results were interpreted as showing that the entry of inositol into the central nervous system from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.

scholarly journals Altered formation and bulk absorption of cerebrospinal fluid in FGF-2-induced hydrocephalus

1999 ◽  
Vol 277 (1) ◽  
pp. R263-R271 ◽  
Author(s):  
C. E. Johanson ◽  
J. Szmydynger-Chodobska ◽  
A. Chodobski ◽  
A. Baird ◽  
P. McMillan ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Formation Rate ◽  
Cerebral Aqueduct ◽  
Sprague Dawley ◽  
Main Site ◽  
Bulk Absorption ◽  
The Central Nervous System ◽  
Fluid Formation ◽  
Csf Absorption ◽  
Csf Formation Rate

Upregulation of certain growth factors in the central nervous system can alter brain fluid dynamics. Hydrocephalus was produced in adult Sprague-Dawley rats by infusing recombinant basic fibroblast growth factor (FGF-2) at 1 μg/day into a lateral ventricle for 2, 3, 5, or 10–12 days. Lateral and third ventricular enlargement progressively increased from 2 to 10 days. Ventriculomegaly was also induced by a 75% reduced dose of FGF-2. At 10–12 days, there was a 29% attenuation in cerebrospinal fluid (CSF) formation rate, from 2.5 to 1.8 μl/min ( P < 0.01). Choroid plexus, the main site of CSF secretion, had an augmented number of dark epithelial cells, which have previously been associated with decreased choroidal fluid formation. The twofold elevated resistance to CSF absorption, i.e., 0.8 to 1.7 mmHg ⋅ min−1 ⋅ μl−1, was attributable, at least in part, to enhanced fibrosis and collagen deposits in the arachnoid villi, a major site for CSF absorption. Normal CSF pressure (2–3 mmHg) was consistent with a patent cerebral aqueduct and reduced CSF formation rate. The FGF-2-induced ventriculomegaly is interpreted as an ex vacuuo hydrocephalus brought about by an altered neuropil and interstitium of the brain.

scholarly journals Modification of K conductance of the squid axon membrane by SITS.

1986 ◽  
Vol 88 (4) ◽  
pp. 507-520 ◽  
Author(s):  
I Inoue
Keyword(s):  
Drug Effects ◽  
Resting Potential ◽  
Disulfonic Acid ◽  
K Channel ◽  
Na Channel ◽  
Axon Membrane ◽  
K Channels ◽  
Disulfonic Stilbene ◽  
Opening And Closing ◽  
Voltage Region

The effects of 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) on the K conductance, gK, were studied in internally perfused giant axons from squid, Doryteuthis. SITS at 3-200 microM was applied intracellularly by adding the reagent to the internal perfusion fluid. Three remarkable changes in gK were noted: there was a slowing of the opening and closing rates of the K channel in the whole voltage region; K channels modified with SITS started to open at voltages below -100 mV, and thus 30% of total K channels were open at the level of normal resting potential (approximately -60 mV) after the maximal drug effect was attained (less than 30 microM); there was a disappearance of gK inactivation that became distinct at relatively high temperature (greater than 8 degrees C). These drug effects depended solely on the drug concentration, not on factors such as repetitive alterations of the membrane potential, and the changes in gK were almost irreversible. Another disulfonic stilbene derivative, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), had similar effects on gK, but the effects were approximately 1.5 times stronger. These changes in gK were somewhat similar to alterations in gNa produced by an application of veratridine, batrachotoxin, and grayanotoxin, which are known as Na channel openers.

Choroid plexus Na+/K+-activated adenosine triphosphatase and cerebrospinal fluid formation

Neurosurgery ◽  
1985 ◽  
Vol 17 (5) ◽  
pp. 768???72 ◽  
Author(s):  
M Pollay ◽  
B Hisey ◽  
E Reynolds ◽  
P Tomkins ◽  
F A Stevens ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Adenosine Triphosphatase ◽  
Fluid Formation

scholarly journals Zika virus infects pericytes in the choroid plexus and enters the central nervous system through the blood-cerebrospinal fluid barrier

2019 ◽  
Author(s):  
Jihye Kim ◽  
Michal Hetman ◽  
Eyas M. Hattab ◽  
Joshua Joiner ◽  
Brian Alejandro ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Zika Virus ◽  
Neurological Complications ◽  
Brain Infection ◽  
The Central Nervous System ◽  
The Brain ◽  
Host Brain

ABSTRACTZika virus (ZIKV) can infect and cause microcephaly and Zika-associated neurological complications in the developing fetal and adult brains. In terms of pathogenesis, a critical question is how ZIKV overcomes the barriers separating the brain from the circulation and gains access to the central nervous system (CNS). Despite the importance of ZIKV pathogenesis, the route ZIKV utilizes to cross CNS barriers remains unclear.Here we show that in mouse models, ZIKV-infected cells initially appeared in the periventricular regions of the brain, including the choroid plexus and the meninges, prior to infection of the cortex. The appearance of ZIKV in cerebrospinal fluid (CSF) preceded infection of the brain parenchyma. We show that ZIKV infects pericytes in the choroid plexus, and that ZIKV infection of pericytes is dependent on AXL receptor tyrosine kinase. Using an in vitro Transwell system, we highlight the possibility of ZIKV to move from the blood side to CSF side, across the choroid plexus epithelial layers, via a nondestructive pathway (e.g., transcytosis). Finally, we demonstrate that brain infection is significantly attenuated by neutralization of the virus in the CSF, indicating that ZIKV in the CSF at the early stage of infection might be responsible for establishing a lethal infection of the brain. Taken together, our results suggest that ZIKV invades the host brain by exploiting the blood-CSF barrier rather than the blood-brain barrier.AUTHOR SUMMARYZika virus invades the human brains and causes Zika-associated neurological complications; however, the mechanism(s) by which Zika virus accesses the central nerves system remain unclear. Understanding of the cellular and molecular mechanisms will shed light on development of novel therapeutic and prophylactic targets for Zika virus and other neurotropic viruses. Here we use in vivo and in vitro models to understand how Zika virus enters the brain. In mouse models, we found that Zika virus infects pericytes in the choroid plexus at very early stages of infection and neutralization of Zika virus in the cerebrospinal fluid significantly attenuate the brain infection. Further we show evidence that Zika virus can cross the epithelial cell layers in the choroid plexus from the blood side. Our research highlights that ZIKV invades the host brain by exploiting the blood-CSF barrier rather than the blood-brain barrier.

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