ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis 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
122 citing papers in PubMed, 1 synthesis or guideline pooled it, 195 citations in OpenAlex.
- Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines.Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2021Guideline
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- Laser interstitial thermal therapy enhances bidirectional blood-brain barrier permeability in glioblastoma.Neuro-oncology · 2026Article
- N-Methyl-D-aspartate receptors: structure, signaling and roles in atherosclerosis.Journal of translational medicine · 2026Review
- Adenosine Signaling in Primary and Metastatic Brain Tumors: Immune Suppression, Tumor Progression, and Therapeutic Opportunities.Molecular neurobiology · 2026Review
- Leveraging neuroscience imaging and electrophysiological assessments to decode neuron-glioma interactions.Neuro-oncology advances · 2026Review
- EndothelialThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Intranasal vs. Device-Assisted Drug Delivery: Advantages and Limitations for the Delivery of Biopharmaceuticals to the CNS.Pharmaceutics · 2026Review
- Pathological Roles of Astrocytes in Traumatic Brain Injury.CNS neuroscience & therapeutics · 2026Review
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- The crosstalk between blood-brain barrier and neural cells: bidirectional regulation of brain function and pathology.Biochemistry and biophysics reports · 2026Review
- Multi-omics analysis reveals metabolic diversity underlying endothelial cell functions.Life science alliance · 2026Article
- Review
- Toothache and Alzheimer's Disease: A Mendelian Randomization Study of the NAAG-CD33 Neuroimmune Axis.Journal of pain research · 2026Article
- The Role of Blood-Brain Barrier Disruption in Epilepsy: Mechanisms and Consequences.Neurology international · 2025Review
- NMDA receptors coordinate brain vascular development via neuron-to-endothelial tip cell crosstalk in zebrafish.Nature communications · 2025Article
- Brain pericytes upregulate glutamate uptake by astrocytesIBRO neuroscience reports · 2025Article
- Dynamic modulation of the blood-brain barrier in the healthy brain.Nature reviews. Neuroscience · 2025Review
- Whispering Through the Barrier: Signaling Interfaces for Peripheral Regulation of Brain Function in Obesity.Journal of neurochemistry · 2025Review
- Blood‑brain barrier dysfunction in epilepsy: Mechanisms, therapeutic strategies and future orientation (Review).International journal of molecular medicine · 2025Review
62 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
19 authors at 5 institutions in 4 countries.
Funding
Abstract
unlabelledThe blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT: In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders.
Indexed as
Identifiers
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.