ReviewFrontiers in neuroscience2015
Markers for blood-brain barrier integrity: how appropriate is Evans blue in the twenty-first century and what are the alternatives?
Review in Frontiers in neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 1 of them a synthesis that pooled it.
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Who cites it
179 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Experimental treatments to attenuate blood spinal cord barrier rupture in rats with traumatic spinal cord injury: A meta-analysis and systematic review.Frontiers in pharmacology · 2022Pooled it
- Biomedical Materials and Fabrication Methods for Construction of In Vitro Neurovascular Unit Models.Materials (Basel, Switzerland) · 2026Review
- Chemogenetic modulation of CNS pericytes: Impact on pericyte CaMolecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Nitric Oxide-S-Nitrosylation and Its Role in Neuroinflammation Associated with Neuropsychiatric Conditions.International journal of molecular sciences · 2026Review
- Novel paracellular marker based on ᴅ-dipeptide structure for highly sensitive quantification with UPLC-MS/MS for in vitro and in vivo blood-brain barrier permeability analysis.Fluids and barriers of the CNS · 2026Article
- Adiponectin deficiency drives cerebrovascular dysfunction and synergizes with amyloid-β to exacerbate alzheimer's pathology.Alzheimer's research & therapy · 2026Article
- Endothelial ferroptosis in blood-brain barrier dysfunction and neuroinflammation: mechanisms and immune-vascular crosstalk.Frontiers in immunology · 2026Review
- Tembusu virus neuroinvasion and neuropathogenesis: lessons from blood-brain barrier dysfunction in neurotropic flaviviruses.Frontiers in veterinary science · 2026Review
- Quantification of immunoglobulin G as an alternative method to the Miles Evans blue assay to measure vascular hyperpermeability induced by infection and sterile inflammation.Biology methods & protocols · 2026Article
- HaloTrace: A spatiotemporally precise fluorescent readout of blood-brain barrier permeability in mice.bioRxiv : the preprint server for biology · 2025Article
- Navigation Between Alzheimer's Disease (AD) and Its Various Pathophysiological Trajectories: The Pathogenic Link to Neuroimmunology-Genetics and Neuroinflammation.International journal of molecular sciences · 2025Review
- Caffeine and Exercise: A Dual Approach to Combat Cognitive Decline Induced by REM Sleep Deprivation.Molecular neurobiology · 2025Article
- Identifying a potential role of immune cells in gadolinium deposition within the brain.Fluids and barriers of the CNS · 2025Article
- Rapid synergistic thrombolysis of ischemic stroke guided by high-resolution and high-speed photoacoustic cerebrovascular imaging.Photoacoustics · 2025Article
- NIR-II Fluorescent Protein Created by In Situ Albumin-Tagging for Sensitive and Specific Imaging of Blood-Brain Barrier Disruption.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Functionally distinct pericyte subsets differently regulate amyloid-β deposition in patients with Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2025Article
- Therapeutic Drug Distribution across the Mouse Brain Is Heterogeneous as Revealed by In Vivo, Spatially Resolved Aptamer-Based Sensing.ACS pharmacology & translational science · 2025Article
- In situ albumin tagging for targeted imaging of endothelial barrier disruption.Science advances · 2025Article
- ROS-regulated SUR1-TRPM4 drives persistent activation of NLRP3 inflammasome in microglia after whole-brain radiation.Acta neuropathologica communications · 2025Article
- Assessment of Blood-Brain Barrier Integrity Using Dyes and Tracers.Methods in molecular biology (Clifton, N.J.) · 2025Article
119 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
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In recent years there has been a resurgence of interest in brain barriers and various roles their intrinsic mechanisms may play in neurological disorders. Such studies require suitable models and markers to demonstrate integrity and functional changes at the interfaces between blood, brain, and cerebrospinal fluid. Studies of brain barrier mechanisms and measurements of plasma volume using dyes have a long-standing history, dating back to the late nineteenth-century. Their use in blood-brain barrier studies continues in spite of their known serious limitations in in vivo applications. These were well known when first introduced, but seem to have been forgotten since. Understanding these limitations is important because Evans blue is still the most commonly used marker of brain barrier integrity and those using it seem oblivious to problems arising from its in vivo application. The introduction of HRP in the mid twentieth-century was an important advance because its reaction product can be visualized at the electron microscopical level, but it also has limitations. Advantages and disadvantages of these markers will be discussed together with a critical evaluation of alternative approaches. There is no single marker suitable for all purposes. A combination of different sized, visualizable dextrans and radiolabeled molecules currently seems to be the most appropriate approach for qualitative and quantitative assessment of barrier integrity.
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