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

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.

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.

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.

scholarly journals Chemical Gradients within Brain Extracellular Space Measured using Low Flow Push–Pull Perfusion Sampling in Vivo

2012 ◽  
Vol 4 (2) ◽  
pp. 321-329 ◽  
Author(s):  
Thomas R. Slaney ◽  
Omar S. Mabrouk ◽  
Kirsten A. Porter-Stransky ◽  
Brandon J. Aragona ◽  
Robert T. Kennedy
Keyword(s):  
Extracellular Space ◽  
Low Flow ◽  
Chemical Gradients ◽  
Brain Extracellular Space

Evolution of Crystallinity in Mixed-Phase (a+μc)-Si:H as Determined by Real Time Spectroscopic Ellipsometry

2003 ◽  
Vol 762 ◽  
Author(s):  
A. S. Ferlauto ◽  
G. M. Ferreira ◽  
R.J. Koval ◽  
J.M. Pearce ◽  
C.R. Wronski ◽  
...  
Keyword(s):  
Real Time ◽  
Spectroscopic Ellipsometry ◽  
Vapor Deposition ◽  
Volume Fraction ◽  
Cone Angle ◽  
Chemical Vapor ◽  
Mixed Phase ◽  
Thin Film Solar Cells ◽  
Nucleation Density ◽  
Microcrystalline Silicon

AbstractThe ability to characterize the phase of the intrinsic (i) layers incorporated into amorphous silicon [a-Si:H] and microcrystalline silicon [μc-Si:H] thin film solar cells is critically important for cell optimization. In our research, a new method has been developed to extract the thickness evolution of the μc-Si:H volume fraction in mixed phase amorphous + microcrystalline silicon [(a+μc)-Si:H] i-layers. This method is based on real time spectroscopic ellipsometry measurements performed during plasma-enhanced chemical vapor deposition of the films. In the analysis, the thickness at which crystallites first nucleate from the a-Si:H phase can be estimated, as well as the nucleation density and microcrystallite cone angle. The results correlate well with structural and solar cell measurements.

scholarly journals Time-resolved quantification of the dynamic extracellular space in the brain during short-lived event: methodology and simulations

2019 ◽  
Vol 121 (5) ◽  
pp. 1718-1734 ◽  
Author(s):  
Kevin C. Chen ◽  
Yi Zhou ◽  
Hui-Hui Zhao
Keyword(s):  
Extracellular Space ◽  
Volume Fraction ◽  
Interelectrode Distance ◽  
Operating Parameters ◽  
High Fidelity ◽  
Phase Lag ◽  
Time Resolved ◽  
Time Pattern ◽  
Waveform Amplitude ◽  
The Brain

Two macroscopic parameters describe the interstitial diffusion of substances in the extracellular space (ECS) of the brain, the ECS volume fraction α and the diffusion tortuosity λ. Past methods based on sampling the extracellular concentration of a membrane-impermeable ion tracer, such as tetramethylammonium (TMA+), can characterize either the dynamic α( t) alone or the constant α and λ in resting state but never the dynamic α( t) and λ( t) simultaneously in short-lived brain events. In this work, we propose to use a sinusoidal method of TMA+ to provide time-resolved quantification of α( t) and λ( t) in acute brain events. This method iontophoretically injects TMA+ in the brain ECS by a sinusoidal time pattern, samples the resulting TMA+ diffusion waveform at a distance, and analyzes the transient modulations of the amplitude and phase lag of the sampled TMA+ waveform to infer α( t) and λ( t). Applicability of the sinusoidal method was verified through computer simulations of the sinusoidal TMA+ diffusion waveform in cortical spreading depression. Parameter sensitivity analysis identified the sinusoidal frequency and the interelectrode distance as two key operating parameters. Compared with other TMA+-based methods, the sinusoidal method can more accurately capture the dynamic α( t) and λ( t) in acute brain events and is equally applicable to other pathological episodes such as epilepsy, transient ischemic attack, and brain injury. Future improvement of the method should focus on high-fidelity extraction of the waveform amplitude and phase angle. NEW & NOTEWORTHY An iontophoretic sinusoidal method of tetramethylammonium is described to capture the dynamic brain extracellular space volume fraction α and diffusion tortuosity λ. The sinusoidal frequency and interelectrode distance are two key operating parameters affecting the method’s accuracy in capturing α( t) and λ( t). High-fidelity extraction of the waveform amplitude and phase lag is critical to successful sinusoidal analyses.

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