ReviewBiophysical journal2017
Brain Extracellular Space: The Final Frontier of Neuroscience.
Review in Biophysical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
166 citing papers in PubMed, 2 syntheses or guidelines pooled it, 317 citations in OpenAlex.
- Peripheral Blood and Salivary Biomarkers of Blood-Brain Barrier Permeability and Neuronal Damage: Clinical and Applied Concepts.Frontiers in neurology · 2020Pooled it
- Pooled it
- Immediate impact of yogic breathing on pulsatile cerebrospinal fluid dynamics.Scientific reports · 2022Trial
- Clinical Soma and Neurite Density Imaging (SANDI): Translational Microstructure Mapping on Clinical 3T MRI Scanners.Magnetic resonance in medicine · 2026Article
- Hypothalamic neurovascular and extracellular matrix remodeling: Cellular niche orchestration of immune-metabolic adaptation to nutritional stress.Reviews in endocrine & metabolic disorders · 2026Review
- Dead-Space Microdomains as Explicit Barriers to Extracellular Drug Transport in Alzheimer's Disease.Pharmaceutical research · 2026Article
- The electrofluidic brain as a basement layer for neural computation.Communications biology · 2026Review
- Tissue oxygenation dynamics during transition from seizure to spreading depolarization in rat brain.Epilepsia · 2026Article
- Quantitative comparison of methods for widespread delivery of small molecules across the blood-brain barrier.Communications biology · 2026Article
- Extracellular space diffusion modelling identifies distinct functional advantages of glutamatergic and GABAergic synapse geometries.Fluids and barriers of the CNS · 2026Article
- Ploidy and neuron size impact nervous system development and function in Xenopus.Cell reports · 2026Article
- Nanoscopic Mapping of the Extracellular Space in Amyloid Plaque-rich Cortex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Brain Extracellular Space: From an Overlooked Dimension to Catalyst of a Novel Neuroscience Paradigm.Cyborg and bionic systems (Washington, D.C.) · 2026Review
- Do enlarged white matter perivascular spaces reflect brain clearance dysfunction? Insights from intrathecal contrast-enhanced MRI.Neuroradiology · 2026Article
- Modified AAV5 capsid for improved brain biodistribution following direct injection in preclinical models.Molecular therapy. Methods & clinical development · 2025Article
- Improving the Detection of Analyte Degeneracies in Untargeted Liquid Chromatography-Tandem Mass Spectrometry Data.Analytical chemistry · 2025Article
- Alzheimer's Tau seeds-induced pathology enhances hippocampal extracellular diffusion.Communications biology · 2025Article
- Differential activity of transcription factors and neuronal effectors during the development of pikeperch brain.Biology open · 2025Article
- Calcium Dynamics in Astrocyte-Neuron Communication from Intracellular to Extracellular Signaling.Cells · 2025Review
- Clioquinol as a new therapy in epilepsy: From preclinical evidence to a proof-of-concept clinical study.Epilepsia · 2025Article
106 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Brain extracellular space is the narrow microenvironment that surrounds every cell of the central nervous system. It contains a solution that closely resembles cerebrospinal fluid with the addition of extracellular matrix molecules. The space provides a reservoir for ions essential to the electrical activity of neurons and forms an intercellular chemical communication channel. Attempts to reveal the size and structure of the extracellular space using electron microscopy have had limited success; however, a biophysical approach based on diffusion of selected probe molecules has proved useful. A point-source paradigm, realized in the real-time iontophoresis method using tetramethylammonium, as well as earlier radiotracer methods, have shown that the extracellular space occupies ∼20% of brain tissue and small molecules have an effective diffusion coefficient that is two-fifths that in a free solution. Monte Carlo modeling indicates that geometrical constraints, including dead-space microdomains, contribute to the hindrance to diffusion. Imaging the spread of macromolecules shows them increasingly hindered as a function of size and suggests that the gaps between cells are predominantly ∼40 nm with wider local expansions that may represent dead-spaces. Diffusion measurements also characterize interactions of ions and proteins with the chondroitin and heparan sulfate components of the extracellular matrix; however, the many roles of the matrix are only starting to become apparent. The existence and magnitude of bulk flow and the so-called glymphatic system are topics of current interest and controversy. The extracellular space is an exciting area for research that will be propelled by emerging technologies.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.