scholarly journals Spatial model of convective solute transport in brain extracellular space does not support a “glymphatic” mechanism

2016 ◽  
Vol 148 (6) ◽  
pp. 489-501 ◽  
Author(s):  
Byung-Ju Jin ◽  
Alex J. Smith ◽  
Alan S. Verkman
Keyword(s):  
Solute Transport ◽  
Water Permeability ◽  
Extracellular Space ◽  
Fluid Transport ◽  
Volume Fraction ◽  
Convective Transport ◽  
Solute Diffusion ◽  
Model Parameters ◽  
Pulsatile Pressure ◽  
Brain Extracellular Space

A “glymphatic system,” which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier–Stokes and convection–diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS.

scholarly journals Aquaporin-4–dependent K+ and water transport modeled in brain extracellular space following neuroexcitation

2012 ◽  
Vol 141 (1) ◽  
pp. 119-132 ◽  
Author(s):  
Byung-Ju Jin ◽  
Hua Zhang ◽  
Devin K. Binder ◽  
A.S. Verkman
Keyword(s):  
Water Transport ◽  
Water Permeability ◽  
Extracellular Space ◽  
Water Channel ◽  
Aquaporin 4 ◽  
Solute Diffusion ◽  
Water Transport Properties ◽  
And Diffusion ◽  
K Permeability ◽  
Brain Extracellular Space

Potassium (K+) ions released into brain extracellular space (ECS) during neuroexcitation are efficiently taken up by astrocytes. Deletion of astrocyte water channel aquaporin-4 (AQP4) in mice alters neuroexcitation by reducing ECS [K+] accumulation and slowing K+ reuptake. These effects could involve AQP4-dependent: (a) K+ permeability, (b) resting ECS volume, (c) ECS contraction during K+ reuptake, and (d) diffusion-limited water/K+ transport coupling. To investigate the role of these mechanisms, we compared experimental data to predictions of a model of K+ and water uptake into astrocytes after neuronal release of K+ into the ECS. The model computed the kinetics of ECS [K+] and volume, with input parameters including initial ECS volume, astrocyte K+ conductance and water permeability, and diffusion in astrocyte cytoplasm. Numerical methods were developed to compute transport and diffusion for a nonstationary astrocyte–ECS interface. The modeling showed that mechanisms b–d, together, can predict experimentally observed impairment in K+ reuptake from the ECS in AQP4 deficiency, as well as altered K+ accumulation in the ECS after neuroexcitation, provided that astrocyte water permeability is sufficiently reduced in AQP4 deficiency and that solute diffusion in astrocyte cytoplasm is sufficiently low. The modeling thus provides a potential explanation for AQP4-dependent K+/water coupling in the ECS without requiring AQP4-dependent astrocyte K+ permeability. Our model links the physical and ion/water transport properties of brain cells with the dynamics of neuroexcitation, and supports the conclusion that reduced AQP4-dependent water transport is responsible for defective neuroexcitation in AQP4 deficiency.

scholarly journals Standing-Gradient Osmotic Flow

1967 ◽  
Vol 50 (8) ◽  
pp. 2061-2083 ◽  
Author(s):  
Jared M. Diamond ◽  
William H. Bossert
Keyword(s):  
Diffusion Coefficient ◽  
Solute Transport ◽  
Water Permeability ◽  
Fluid Transport ◽  
Distal Tubule ◽  
Channel Length ◽  
Transport Rate ◽  
Solute Diffusion ◽  
Gradient System ◽  
Wide Range

At the ultrastructural level, epithelia performing solute-linked water transport possess long, narrow channels open at one end and closed at the other, which may constitute the fluid transport route (e.g., lateral intercellular spaces, basal infoldings, intracellular canaliculi, and brush-border microvilli). Active solute transport into such folded structures would establish standing osmotic gradients, causing a progressive approach to osmotic equilibrium along the channel's length. The behavior of a simple standing-gradient flow system has therefore been analyzed mathematically because of its potential physiological significance. The osmolarity of the fluid emerging from the channel's open end depends upon five parameters: channel length, radius, and water permeability, and solute transport rate and diffusion coefficient. For ranges of values of these parameters encountered experimentally in epithelia, the emergent osmolarity is found by calculation to range from isotonic to a few times isotonic; i.e., the range encountered in epithelial absorbates and secretions. The transported fluid becomes more isotonic as channel radius or solute diffusion coefficient is decreased, or as channel length or water permeability is increased. Given appropriate parameters, a standing-gradient system can yield hypertonic fluids whose osmolarities are virtually independent of transport rate over a wide range, as in distal tubule and avian salt gland. The results suggest that water-to-solute coupling in epithelia is due to the ultrastructural geometry of the transport route.

Changes of Peritoneal Transport Parameters with Time on Dialysis: Assessment with Sequential Peritoneal Equilibration Test

2017 ◽  
Vol 40 (11) ◽  
pp. 595-601 ◽  
Author(s):  
Jacek Waniewski ◽  
Stefan Antosiewicz ◽  
Daniel Baczynski ◽  
Jan Poleszczuk ◽  
Mauro Pietribiasi ◽  
...  
Keyword(s):  
Solute Transport ◽  
Fluid Transport ◽  
Transport Processes ◽  
Model Parameters ◽  
Hydraulic Permeability ◽  
Transport Parameters ◽  
Peritoneal Equilibration Test ◽  
Transport Barrier ◽  
Pore Model ◽  
Peritoneal Transport

Background Sequential peritoneal equilibration test (sPET) is based on the consecutive performance of the peritoneal equilibration test (PET, 4-hour, glucose 2.27%) and the mini-PET (1-hour, glucose 3.86%), and the estimation of peritoneal transport parameters with the 2-pore model. It enables the assessment of the functional transport barrier for fluid and small solutes. The objective of this study was to check whether the estimated model parameters can serve as better and earlier indicators of the changes in the peritoneal transport characteristics than directly measured transport indices that depend on several transport processes. Methods 17 patients were examined using sPET twice with the interval of about 8 months (230 ± 60 days). Results There was no difference between the observational parameters measured in the 2 examinations. The indices for solute transport, but not net UF, were well correlated between the examinations. Among the estimated parameters, a significant decrease between the 2 examinations was found only for hydraulic permeability LpS, and osmotic conductance for glucose, whereas the other parameters remained unchanged. These fluid transport parameters did not correlate with D/P for creatinine, although the decrease in LpS values between the examinations was observed mostly for patients with low D/P for creatinine. Conclusions We conclude that changes in fluid transport parameters, hydraulic permeability and osmotic conductance for glucose, as assessed by the pore model, may precede the changes in small solute transport. The systematic assessment of fluid transport status needs specific clinical and mathematical tools beside the standard PET tests.

scholarly journals Real-time Iontophoresis with Tetramethylammonium to Quantify Volume Fraction and Tortuosity of Brain Extracellular Space

10.3791/55755 ◽  
2017 ◽  
Author(s):  
John Odackal ◽  
Robert Colbourn ◽  
Namrita Jain Odackal ◽  
Lian Tao ◽  
Charles Nicholson ◽  
...  
Keyword(s):  
Real Time ◽  
Extracellular Space ◽  
Volume Fraction ◽  
Brain Extracellular Space

Quantitative analysis of extracellular space using the method of TMA+ iontophoresis and the issue of TMA+ uptake

1992 ◽  
Vol 70 (S1) ◽  
pp. S314-S322 ◽  
Author(s):  
Charles Nicholson
Keyword(s):  
Spatial Distribution ◽  
Extracellular Space ◽  
Final Section ◽  
Volume Fraction ◽  
Time Data ◽  
Temporal And Spatial Distribution ◽  
Temporal And Spatial ◽  
The Given ◽  
Brain Extracellular Space ◽  
Space Volume

The tetramethylammonium (TMA+) method for measuring the volume fraction and tortuosity of brain extracellular space is presented in detail. The temporal and spatial distribution of TMA+ in the extracellular space following iontophoresis or pressure microinjection is described by suitable equations and illustrated with graphs. By fitting the equations to the concentration versus time data obtained from measurements with ion-selective micropipettes, the volume fraction and tortuosity can be measured. In addition, the concentration-dependent uptake of TMA+ can be estimated from the given equations. The final section of the paper derives simple numerical estimates of TMA+ loss from the extracellular space by this mechanism.Key words: extracellular space, volume fraction, tortuosity, uptake, tetramethylammonium.

Dynamic Modeling of Channel Formation During Fluid Injection Into Unconsolidated Formations

SPE Journal ◽  
2015 ◽  
Vol 20 (04) ◽  
pp. 689-700 ◽  
Author(s):  
S.. Ameen ◽  
A. Dahi Taleghani
Keyword(s):  
Preferential Flow ◽  
Volume Fraction ◽  
Injection Pressure ◽  
Internal Erosion ◽  
Fluid Injection ◽  
Critical Threshold ◽  
Model Parameters ◽  
Flow Paths ◽  
Preferential Flow Paths ◽  
Stress Changes

Summary Injectivity loss is a common problem in unconsolidated-sand formations. Injection of water into a poorly cemented granular medium may lead to internal erosion, and consequently formation of preferential flow paths within the medium because of channelization. Channelization in the porous medium might occur when fluid-induced stresses become locally larger than a critical threshold and small grains are dislodged and carried away; hence, porosity and permeability of the medium will evolve along the induced flow paths. Vice versa, flowback during shut-in might carry particles back to the well and cause sand accumulation inside the well, and subsequently loss of injectivity. In most cases, to maintain the injection rate, operators will increase injection pressure and pumping power. The increased injection pressure results in stress changes and possibly further changes in channel patterns around the wellbore. Experimental laboratory studies have confirmed the presence of the transition from uniform Darcy flow to a fingered-pattern flow. To predict these phenomena, a model is needed to fill this gap by predicting the formation of preferential flow paths and their evolution. A model based on the multiphase-volume-fraction concept is used to decompose porosity into mobile and immobile porosities where phases may change spatially, evolve over time, and lead to development of erosional channels depending on injection rates, viscosity, and rock properties. This model will account for both particle release and suspension deposition. By use of this model, a methodology is proposed to derive model parameters from routine injection tests by inverse analysis. The proposed model presents the characteristic behavior of unconsolidated formation during fluid injection and the possible effect of injection parameters on downhole-permeability evolution.

scholarly journals Glutamate, NMDA, and AMPA Induced Changes in Extracellular Space Volume and Tortuosity in the Rat Spinal Cord

2001 ◽  
Vol 21 (9) ◽  
pp. 1077-1089 ◽  
Author(s):  
Lýdia Vargová ◽  
Pavla Jendelová ◽  
Alexandr Chvátal ◽  
Eva Syková
Keyword(s):  
Spinal Cord ◽  
Glutamate Receptor ◽  
Extracellular Space ◽  
Volume Fraction ◽  
Glutamate Release ◽  
Extracellular Potassium ◽  
Receptor Agonists ◽  
Diffusion Parameters ◽  
Glutamate Receptor Agonists ◽  
Cellular Swelling

Glutamate release, particularly in pathologic conditions, may result in cellular swelling. The authors studied the effects of glutamate, N-methyl-d-aspartate (NMDA), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) on extracellular pH (pHe), extracellular potassium concentration ([K+]e), and changes in extracellular space (ECS) diffusion parameters (volume fraction α, tortuosity λ) resulting from cellular swelling. In the isolated spinal cord of 4-to 12-day-old rats, the application of glutamate receptor agonists induced an increase in [K+]e, alkaline-acid shifts, a substantial decrease in α, and an increase in λ. After washout of the glutamate receptor agonists, α either returned to or overshot normal values, whereas λ remained elevated. Pretreatment with 20 mmol/L Mg++, MK801, or CNQX blocked the changes in diffusion parameters, [K+]e and pHe evoked by NMDA or AMPA. However, the changes in diffusion parameters also were blocked in Ca2+-free solution, which had no effect on the [K+]e increase or acid shift. The authors conclude that increased glutamate release may produce a large, sustained and [Ca2+]e-dependent decrease in α and increase in λ. Repetitive stimulation and pathologic states resulting in glutamate release therefore may lead to changes in ECS volume and tortuosity, affecting volume transmission and enhancing glutamate neurotoxicity and neuronal damage.

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