ArticleThe American journal of clinical nutrition2009
The blood-brain barrier and glutamate.
Article in The American journal of clinical nutrition, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
121 citing papers in PubMed, 3 syntheses or guidelines pooled it, 287 citations in OpenAlex.
- Convergent blood-brain barrier breakdown in schizophrenia and autism spectrum disorders: a systematic review of preclinical animal models.Fluids and barriers of the CNS · 2026Pooled it
- Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review.Journal of neurodevelopmental disorders · 2025Pooled it
- Evaluation of Metabolic and Synaptic Dysfunction Hypotheses of Alzheimer's Disease (AD): A Meta-Analysis of CSF Markers.Current Alzheimer research · 2018Pooled it
- Metabolite concentration changes associated with positive and negative BOLD responses in the human visual cortex: A functional MRS study at 7 Tesla.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Trial
- Serum metabolomic profiling identifies a biomarker panel associated with age-related hearing loss.Biochemistry and biophysics reports · 2026Article
- Review
- Berberine attenuates hyperglycemia induced neurodegeneration in mice by modulation of Nrf2 expression.Molecular biology reports · 2026Article
- Central and peripheral glutamatergic biomarkers delineate heterogeneous clinical phenotypes in olanzapine-treated schizophrenia.Scientific reports · 2026Observational
- Structure and enzymology of glutaminase S482C and H461L variants associated with excess brain glutamate and neurological disease.The Journal of biological chemistry · 2026Article
- Gut microbiome community structure correlates with different behavioral phenotypes in the Belyaev Farm-Fox Experiment.Communications biology · 2026Article
- The metabolic layer of cognition: integrating metabolomics, breathomics, and systems neuroscience.Frontiers in neuroscience · 2026Review
- Universal Platform Based on Carbon Nanotubes Functionalised with Carboxylic Acid Groups for Multi-Analyte Enzymatic Biosensing.Biosensors · 2025Article
- Structure and enzymology of glutaminase mutants that disrupt glutamine-glutamate homeostasis and cause neurological disease.bioRxiv : the preprint server for biology · 2025Article
- Unmasking the relationship between CGRP and glutamate: from peripheral excitation to central sensitization in migraine.The journal of headache and pain · 2025Review
- Glutamate/GABA/glutamine ratios in intact and ischemia reperfusion challenged rat brain subregions, the effect of ischemic preconditioning.Metabolic brain disease · 2025Article
- Agonism of the glutamate receptor GluK2 suppresses dermal mast cell activation and cutaneous inflammation.Science translational medicine · 2024Article
- Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus.Brain sciences · 2024Article
- Metabolite and protein associations with general health in the population-based CHRIS study.Scientific reports · 2024Article
- A novel multivariable Mendelian randomization framework to disentangle highly correlated exposures with application to metabolomics.American journal of human genetics · 2024Article
- Review
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Glutamate concentrations in plasma are 50-100 micromol/L; in whole brain, they are 10,000-12,000 micromol/L but only 0.5-2 micromol/L in extracellular fluids (ECFs). The low ECF concentrations, which are essential for optimal brain function, are maintained by neurons, astrocytes, and the blood-brain barrier (BBB). Cerebral capillary endothelial cells form the BBB that surrounds the entire central nervous system. Tight junctions connect endothelial cells and separate the BBB into luminal and abluminal domains. Molecules entering or leaving the brain thus must pass 2 membranes, and each membrane has distinct properties. Facilitative carriers exist only in luminal membranes, and Na(+)-dependent glutamate cotransporters (excitatory amino acid transporters; EAATs) exist exclusively in abluminal membranes. The EAATs are secondary transporters that couple the Na(+) gradient between the ECF and the endothelial cell to move glutamate against the existing electrochemical gradient. Thus, the EAATs in the abluminal membrane shift glutamate from the ECF to the endothelial cell where glutamate is free to diffuse into blood on facilitative carriers. This organization does not allow net glutamate entry to the brain; rather, it promotes the removal of glutamate and the maintenance of low glutamate concentrations in the ECF. This explains studies that show that the BBB is impermeable to glutamate, even at high concentrations, except in a few small areas that have fenestrated capillaries (circumventricular organs). Recently, the question of whether the BBB becomes permeable in diabetes has arisen. This issue was tested in rats with diet-induced obesity and insulin resistance or with streptozotocin-induced diabetes. Neither condition produced any detectable effect on BBB glutamate transport.
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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.