ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Zn2+ influx is critical for some forms of spreading depression in brain slices.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
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Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 100 citations in OpenAlex.
- Effect of ouabain on calcium signaling in rodent brain: A systematic review ofFrontiers in pharmacology · 2022Pooled it
- Systematic review of the pharmacological agents that have been tested against spreading depolarizations.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Pooled it
- Effect of Locally Delivered Nimodipine Microparticles on Spreading Depolarization in Aneurysmal Subarachnoid Hemorrhage.Neurocritical care · 2021Trial
- Computer models predict differential dendritic vulnerability with ischemia and spreading depression.PLoS computational biology · 2026Article
- Zinc dyshomeostasis, mitochondrial dysfunction, and their pathological cycle in ischemic stroke pathophysiology: Mechanisms and potential therapeutic targets.Redox biology · 2026Review
- Article
- Similarities in the Electrographic Patterns of Delayed Cerebral Infarction and Brain Death After Aneurysmal and Traumatic Subarachnoid Hemorrhage.Translational stroke research · 2025Review
- All Three Supersystems-Nervous, Vascular, and Immune-Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage.Translational stroke research · 2025Review
- Organellular imagingbioRxiv : the preprint server for biology · 2024Article
- From spreading depolarization to blood-brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy.Nature reviews. Neurology · 2024Review
- Isoflurane lowers the cerebral metabolic rate of oxygen and prevents hypoxia during cortical spreading depolarizationJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Synaptic ZnNeurobiology of disease · 2024Article
- Synaptic ZnbioRxiv : the preprint server for biology · 2023Article
- Plasticity of perisynaptic astroglia during ischemia-induced spreading depolarization.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Questioning Glutamate Excitotoxicity in Acute Brain Damage: The Importance of Spreading Depolarization.Neurocritical care · 2022Article
- The Relationship Between Seizures and Spreading Depolarizations in Patients with Severe Traumatic Brain Injury.Neurocritical care · 2022Observational
- Cortical spreading depression: culprits and mechanisms.Experimental brain research · 2022Review
- Migraine Aura, Transient Ischemic Attacks, Stroke, and Dying of the Brain Share the Same Key Pathophysiological Process in Neurons Driven by Gibbs-Donnan Forces, Namely Spreading Depolarization.Frontiers in cellular neuroscience · 2022Review
- The Function and Regulation of Zinc in the Brain.Neuroscience · 2021Review
- Alzheimer risk factors age and female sex induce cortical Aβ aggregation by raising extracellular zinc.Molecular psychiatry · 2020Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Spreading depression (SD) is wave of profound depolarization that propagates throughout brain tissue and can contribute to the spread of injury after stroke or traumatic insults. The contribution of Ca(2+) influx to SD differs depending on the stimulus, and we show here that Zn(2+) can play a critical complementary role in murine hippocampal slices. In initial studies, we used the Na(+)/K(+) ATPase inhibitor ouabain and found conditions in which SD was always prevented by L-type Ca(2+) channel blockers; however, Ca(2+) influx was not responsible for L-type effects. Cytosolic Ca(2+) increases were not detectable in CA1 neurons before SD, and removal of extracellular Ca(2+) did not prevent ouabain-SD. In contrast, cytosolic Zn(2+) increases were observed in CA1 neurons before ouabain-SD, and L-type channel block prevented the intracellular Zn(2+) rises. A slow mitochondrial depolarization observed before ouabain-SD was abolished by L-type channel block, and Zn(2+) accumulation contributed substantially to initial mitochondrial depolarizations. Selective chelation of Zn(2+) with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) abolished SD, implying that Zn(2+) entry can play a critical role in the generation of ouabain-SD. TPEN was most effective when synaptic activity was reduced by adenosine A(1) receptor activation, and a combination of Ca(2+) and Zn(2+) removal was required to prevent ouabain-SD when A(1) receptors were blocked. Similarly, Zn(2+) chelation could prevent SD triggered by oxygen/glucose deprivation but Zn(2+) accumulation did not contribute to SD triggered by localized high K(+) exposures. These results identify Zn(2+) as a new target for the block of spreading depolarizations after brain injury.
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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.