ArticleJournal of visualized experiments : JoVE2017
Real-time Iontophoresis with Tetramethylammonium to Quantify Volume Fraction and Tortuosity of Brain Extracellular Space.
Article in Journal of visualized experiments : JoVE, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Nanoscopic Mapping of the Extracellular Space in Amyloid Plaque-rich Cortex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Aβ Deposition in Extracellular Space Disrupts Glial-Neuron Communication and Triggers Alzheimer's Disease.Aging and disease · 2025Review
- Miniaturized Iontronic Micropipettes for Precise and Dynamic Ionic Modulation of Neuronal and Astrocytic Activity.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Article
- Remote Regulation of Molecular Diffusion in Extracellular Space of Parkinson's Disease Rat Model by Subthalamic Nucleus Deep Brain Stimulation.Cyborg and bionic systems (Washington, D.C.) · 2025Article
- Formaldehyde initiates memory and motor impairments under weightlessness condition.NPJ microgravity · 2024Review
- Lessons on brain edema in HE: from cellular to animal models and clinical studies.Metabolic brain disease · 2024Review
- BubbleDrive, a low-volume incubation chamber for acute brain slices.Scientific reports · 2023Article
- Sheet and void porous media models for brain interstitial space.Journal of the Royal Society, Interface · 2023Article
- Loss of aquaporin-4 results in glymphatic system dysfunction via brain-wide interstitial fluid stagnation.eLife · 2023Article
- Intercellular Communication in the Central Nervous System as Deduced by Chemical Neuroanatomy and Quantitative Analysis of Images: Impact on Neuropharmacology.International journal of molecular sciences · 2022Review
- Effect of Particle Size and Surface Charge on Nanoparticles Diffusion in the Brain White Matter.Pharmaceutical research · 2022Article
- Engineered cell culture microenvironments for mechanobiology studies of brain neural cells.Frontiers in bioengineering and biotechnology · 2022Review
- Rapid volume pulsation of the extracellular space coincides with epileptiform activity in mice and depends on the NBCe1 transporter.The Journal of physiology · 2021Article
- Reduction of Dimensionality in Monte Carlo Simulation of Diffusion in Extracellular Space Surrounding Cubic Cells.Neurochemical research · 2020Article
- Current Techniques for Investigating the Brain Extracellular Space.Frontiers in neuroscience · 2020Review
- Integrity of White Matter is Compromised in Mice with Hyaluronan Deficiency.Neurochemical research · 2020Article
- Time-Resolved Integrative Optical Imaging of Diffusion during Spreading Depression.Biophysical journal · 2019Article
- ECS Dynamism and Its Influence on Neuronal Excitability and Seizures.Neurochemical research · 2019Review
- Unveiling the Extracellular Space of the Brain: From Super-resolved Microstructure toThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
This review describes the basic concepts and protocol to perform the real-time iontophoresis (RTI) method, the gold-standard to explore and quantify the extracellular space (ECS) of the living brain. The ECS surrounds all brain cells and contains both interstitial fluid and extracellular matrix. The transport of many substances required for brain activity, including neurotransmitters, hormones, and nutrients, occurs by diffusion through the ECS. Changes in the volume and geometry of this space occur during normal brain processes, like sleep, and pathological conditions, like ischemia. However, the structure and regulation of brain ECS, particularly in diseased states, remains largely unexplored. The RTI method measures two physical parameters of living brain: volume fraction and tortuosity. Volume fraction is the proportion of tissue volume occupied by ECS. Tortuosity is a measure of the relative hindrance a substance encounters when diffusing through a brain region as compared to a medium with no obstructions. In RTI, an inert molecule is pulsed from a source microelectrode into the brain ECS. As molecules diffuse away from this source, the changing concentration of the ion is measured over time using an ion-selective microelectrode positioned roughly 100 µm away. From the resulting diffusion curve, both volume fraction and tortuosity can be calculated. This technique has been used in brain slices from multiple species (including humans) and in vivo to study acute and chronic changes to ECS. Unlike other methods, RTI can be used to examine both reversible and irreversible changes to the brain ECS in real time.
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