ArticleFluids and barriers of the CNS2022
Activation of NMDA receptors in brain endothelial cells increases transcellular permeability.
Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
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- Nanotechnology for efficient delivery of TCM active ingredients in treating brain diseases.Materials today. Bio · 2026Review
- Adenosine Signaling in Primary and Metastatic Brain Tumors: Immune Suppression, Tumor Progression, and Therapeutic Opportunities.Molecular neurobiology · 2026Review
- Multiple sevoflurane exposures in early development lead to long-term vascular abnormalities in the hippocampus.Cell biology and toxicology · 2026Article
- EndothelialThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Regeneration-Associated Factors in the Regulation of Adult and Post-Traumatic Neurogenesis in the Forebrain of Fish and Other Vertebrates.International journal of molecular sciences · 2025Review
- Perioperative neurocognitive disorders: Advances in molecular mechanisms and bioactive molecules.Ageing research reviews · 2025Review
- Article
- Blood‑brain barrier dysfunction in epilepsy: Mechanisms, therapeutic strategies and future orientation (Review).International journal of molecular medicine · 2025Review
- Multi-omics Study of Hypoxic-Ischemic Brain Injury After Cardiopulmonary Resuscitation in Swine.Neurocritical care · 2025Article
- Endothelium glutamate receptors in brain pathology.Frontiers in pharmacology · 2025Review
- The ion transport, GPCR, and RTK toolkit expression in the human cerebrovascular endothelial cell line, hCMEC/D3: an Omics perspective.Frontiers in physiology · 2025Article
- Excitotoxic Storms of Ischemic Stroke: A Non-neuronal Perspective.Molecular neurobiology · 2024Review
- The role of endothelial frequency in the cerebral blood flow control during neonatal asphyxia: a retrospective longitudinal study.BMC pediatrics · 2024Article
- NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes.International journal of molecular sciences · 2024Review
- Inhibiting Caveolin-1-Related Akt/mTOR Signaling Pathway Protects Against N-methyl-D-Aspartate Receptor Activation-Mediated Dysfunction of Blood-Brain Barrier in vitro.Molecular neurobiology · 2024Article
- Review
- Anoxia-induced hippocampal LTP is regeneratively produced by glutamate and nitric oxide from the neuro-glial-endothelial axis.iScience · 2024Article
- Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age.Biomedicines · 2024Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurovascular coupling is a precise mechanism that induces increased blood flow to activated brain regions, thereby providing oxygen and glucose. In this study, we hypothesized that N-methyl-D-aspartate (NMDA) receptor signaling, the most well characterized neurotransmitter signaling system which regulates delivery of essential molecules through the blood-brain barrier (BBB). Upon application of NMDA in both in vitro and in vivo models, increased delivery of bioactive molecules that was mediated through modulation of molecules involved in molecular delivery, including clathrin and caveolin were observed. Also, NMDA activation induced structural changes in the BBB and increased transcellular permeability that showed regional heterogeneity in its responses. Moreover, NMDA receptor activation increased endosomal trafficking and facilitated inactivation of lysosomal pathways and consequently increased molecular delivery mediated by activation of calmodulin-dependent protein kinase II (CaMKII) and RhoA/protein kinase C (PKC). Subsequent in vivo experiments using mice specifically lacking NMDA receptor subunit 1 in endothelial cells showed decreased neuronal density in the brain cortex, suggesting that a deficiency in NMDA receptor signaling in brain endothelial cells induces neuronal losses. Together, these results highlight the importance of NMDA-receptor-mediated signaling in the regulation of BBB permeability that surprisingly also affected CD31 staining.
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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 Socratic graph.