ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2013
Regenerative glutamate release by presynaptic NMDA receptors contributes to spreading depression.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Leptin: role over central nervous system in epilepsy.BMC neuroscience · 2018Pooled it
- Glutamate levels and perfusion in pons during migraine attacks: A 3T MRI study using proton spectroscopy and arterial spin labeling.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Trial
- Spreading depolarization: A wave that precedes and drives cerebral ischemic cell death-Target for neuroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Cortical spreading depolarizations in stroke: Mechanisms, neuroprotective interventions, and monitoring techniques.GeroScience · 2026Review
- Review
- Spreading depolarization in neurocritical care: a review of SD'S pathophysiological continuum and clinical translation.Frontiers in human neuroscience · 2026Review
- Intranasal delivery of the NMDA receptor antagonist MK-801 attenuates ultra-acute excitotoxic neurochemical responses after concussion in rats: comparative pharmacological evaluation against ketamine.Frontiers in pharmacology · 2026Article
- The Role of Purinergic Mechanisms in the Excitability of Trigeminal Afferents of Rats with Prenatal Hyperhomocysteinemia.Biomolecules · 2025Article
- Association of plasma soluble urokinase plasminogen activator receptor concentrations and migraine with aura: a REFORM study.Brain communications · 2025Article
- Glutamate load fosters spreading depolarization under osmotic stress in brain slices.Frontiers in cellular neuroscience · 2025Article
- Spreading depolarizations pose critical energy challenges in acute brain injury.Journal of neurochemistry · 2024Review
- Migraine - a borderland disease to epilepsy: near it but not of it.The journal of headache and pain · 2024Review
- Meningeal Mechanisms and the Migraine Connection.Annual review of neuroscience · 2023Review
- Article
- Plasticity of perisynaptic astroglia during ischemia-induced spreading depolarization.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Amyloid AβInternational journal of molecular sciences · 2022Article
- Glutamate and GABASignal transduction and targeted therapy · 2022Article
- Questioning Glutamate Excitotoxicity in Acute Brain Damage: The Importance of Spreading Depolarization.Neurocritical care · 2022Article
- The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention.Neurocritical care · 2022Review
- The Relationship Between Seizures and Spreading Depolarizations in Patients with Severe Traumatic Brain Injury.Neurocritical care · 2022Observational
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Spreading depression (SD) is a slowly propagating neuronal depolarization that underlies certain neurologic conditions. The wave-like pattern of its propagation suggests that SD arises from an unusual form of neuronal communication. We used enzyme-based glutamate electrodes to show that during SD induced by transiently raising extracellular K(+) concentrations ([K(+)]o) in rat brain slices, there was a rapid increase in the extracellular glutamate concentration that required vesicular exocytosis but unlike fast synaptic transmission, still occurred when voltage-gated sodium and calcium channels (VGSC and VGCC) were blocked. Instead, presynaptic N-methyl-D-aspartate (NMDA) receptors (NMDARs) were activated during SD and could generate substantial glutamate release to support regenerative glutamate release and propagating waves when VGSCs and VGCCs were blocked. In calcium-free solutions, high [K(+)]o still triggered SD-like waves and glutamate efflux. Under such a condition, glutamate release was blocked by mitochondrial Na(+)/Ca(2+) exchanger inhibitors that likely blocked calcium release from mitochondria secondary to NMDA-induced Na(+) influx. Therefore presynaptic NMDA receptor activation is sufficient for triggering vesicular glutamate release during SD via both calcium entry and release from mitochondria by mitochondrial Na(+)/Ca(2+) exchanger. Our observations suggest that presynaptic NMDARs contribute to a cycle of glutamate-induced glutamate release that mediate high [K(+)]o-triggered SD.
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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.