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.

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.

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.

scholarly journals Effects of Arterial Pco2 and Cerebrospinal Fluid Volume Flow Rate Changes on Choroid Plexus and Cerebral Blood Flow in Normal and Experimental Hydrocephalic Cats

1983 ◽  
Vol 3 (3) ◽  
pp. 369-375 ◽  
Author(s):  
S. Nakamura ◽  
G. M. Hochwald
Keyword(s):  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Cerebral Cortex ◽  
Choroid Plexus ◽  
Flow Rate ◽  
Volume Flow Rate ◽  
Volume Flow ◽  
Brain Blood Flow ◽  
Choroidal Blood Flow ◽  
Flow Rates

The effect of changes in brain blood flow on cerebrospinal fluid (CSF) volume flow rates, and that of changes in CSF volume flow rates on brain blood flow were determined in both normal and kaolin-induced hydrocephalic cats. In both groups of cats, blood flow in grey and white matter, cerebral cortex, and choroid plexus was measured with 105Ru microspheres during normocapnia, and again with 141Ce microspheres after arterial Pco2 was either increased by 300% or decreased by 50%. Blood flow measurements were also made during perfusion of the ventricular system with mock CSF and repeated during perfusion with anisosmotic mannitol solutions to alter CSF volume flow rate. In 30 normal and 26 hydrocephalic cats, blood flow to the cerebral cortex, white matter, and choroid plexus was similar; only blood flow to the caudate nucleus was greater in normal cats. The weight of the choroid plexus from hydrocephalic cats decreased by 17%. Blood flow in the choroid plexus of all cats decreased by almost 50% following hypercapnia or hypocapnia, without a change in the CSF volume flow rate. There was no change in cerebral or choroidal blood flow when CSF volume flow rate was either increased by 170% or decreased by 80%. These results suggest that choroid plexus blood flow does not limit or affect the volume flow rate of CSF from the choroid plexus. CSF volume flow rate can be altered without corresponding blood flow changes of the brain or choroid plexus. Choroid plexus blood flow and the reactivity of both brain and choroidal blood flow to changes in arterial Pco2 were not affected by the hydrocephalus. The lower CSF formation rate of hydrocephalic cats can be attributed in part to the decrease in the mass of choroid plexus tissue.

Does Aerobic Respiration Produce Carbon Dioxide or Hydrogen Ion and Bicarbonate?

2018 ◽  
Vol 128 (5) ◽  
pp. 873-879 ◽  
Author(s):  
Erik R. Swenson
Keyword(s):  
Carbon Dioxide ◽  
Carbonic Anhydrase ◽  
Intracellular Ph ◽  
Ph Regulation ◽  
Krebs Cycle ◽  
Brain Homogenate ◽  
Hydrogen Ion ◽  
Facilitated Diffusion ◽  
Intracellular Acidosis ◽  
End Products

Abstract Maintenance of intracellular pH is critical for clinical homeostasis. The metabolism of glucose, fatty acids, and amino acids yielding the generation of adenosine triphosphate in the mitochondria is accompanied by the production of acid in the Krebs cycle. Both the nature of this acidosis and the mechanism of its disposal have been argued by two investigators with a long-abiding interest in acid–base physiology. They offer different interpretations and views of the molecular mechanism of this intracellular pH regulation during normal metabolism. Dr. John Severinghaus has posited that hydrogen ion and bicarbonate are the direct end products in the Krebs cycle. In the late 1960s, he showed in brain and brain homogenate experiments that acetazolamide, a carbonic anhydrase inhibitor, reduces intracellular pH. This led him to conclude that hydrogen ion and bicarbonate are the end products, and the role of intracellular carbonic anhydrase is to rapidly generate diffusible carbon dioxide to minimize acidosis. Dr. Erik Swenson posits that carbon dioxide is a direct end product in the Krebs cycle, a more widely accepted view, and that acetazolamide prevents rapid intracellular bicarbonate formation, which can then codiffuse with carbon dioxide to the cell surface and there be reconverted for exit from the cell. Loss of this “facilitated diffusion of carbon dioxide” leads to intracellular acidosis as the still appreciable uncatalyzed rate of carbon dioxide hydration generates more protons. This review summarizes the available evidence and determines that resolution of this question will require more sophisticated measurements of intracellular pH with faster temporal resolution.

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.

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

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.

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