ArticleJournal of neurophysiology2012
Synaptic release and extracellular actions of Zn2+ limit propagation of spreading depression and related events in vitro and in vivo.
Article in Journal of neurophysiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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
22 citing papers in PubMed, 31 citations in OpenAlex.
- Metal Ions Within the Neuro-Immune-Tumor Axis.Journal of immunology research · 2026Review
- Significance of Neurotransmitters in Cerebral Ischemia: Understanding the Role of Serotonin, Dopamine, Glutamate, and GABA in Stroke Recovery and Treatment.Central nervous system agents in medicinal chemistry · 2025Review
- Ketamine improves neuronal recovery following spreading depolarization in peri-infarct tissues.Journal of neurochemistry · 2024Article
- Synaptic ZnNeurobiology of disease · 2024Article
- Synaptic ZnbioRxiv : the preprint server for biology · 2023Article
- Mechanisms of initiation of cortical spreading depression.The journal of headache and pain · 2023Article
- Is the Human Touch Always Therapeutic? Patient Stimulation and Spreading Depolarization after Acute Neurological Injuries.Translational stroke research · 2023Observational
- Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Repetitive spreading depolarization induces gene expression changes related to synaptic plasticity and neuroprotective pathways.Frontiers in cellular neuroscience · 2023Article
- The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention.Neurocritical care · 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
- CaChannels (Austin, Tex.) · 2020Review
- Understanding Spreading Depression from Headache to Sudden Unexpected Death.Frontiers in neurology · 2018Review
- Effects of interleukin-1ß on cortical spreading depolarization and cerebral vasculature.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Neuronal pannexin-1 channels are not molecular routes of water influx during spreading depolarization-induced dendritic beading.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- The ZnBiochimica et biophysica acta. Molecular basis of disease · 2017Article
- Chloride Cotransporters as a Molecular Mechanism underlying Spreading Depolarization-Induced Dendritic Beading.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Chaos and commotion in the wake of cortical spreading depression and spreading depolarizations.Nature reviews. Neuroscience · 2014Review
- Characterization of inhibitory GABA-A receptor activation during spreading depolarization in brain slice.PloS one · 2014Article
- Intracellular Zn2+ accumulation enhances suppression of synaptic activity following spreading depolarization.Journal of neurochemistry · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cortical spreading depression (CSD) is a consequence of a slowly propagating wave of neuronal and glial depolarization (spreading depolarization; SD). Massive release of glutamate contributes to SD propagation, and it was recently shown that Zn(2+) is also released from synaptic vesicles during SD. The present study examined consequences of extracellular Zn(2+) accumulation on the propagation of SD. SD mechanisms were studied first in murine brain slices, using focal KCl applications as stimuli and making electrical and optical recordings in hippocampal area CA1. Elevating extracellular Zn(2+) concentrations with exogenous ZnCl(2) reduced SD propagation rates. Selective chelation of endogenous Zn(2+) (using TPEN or CaEDTA) increased SD propagation rates, and these effects appeared due to chelation of Zn(2+) derived from synaptic vesicles. Thus, in tissues where synaptic Zn(2+) release was absent [knockout (KO) of vesicular Zn(2+) transporter ZnT-3], SD propagation rates were increased, and no additional increase was observed following chelation of endogenous Zn(2+) in these tissues. The role of synaptic Zn(2+) was then examined on CSD in vivo. ZnT-3 KO animals had higher susceptibility to CSD than wild-type controls as evidenced by significantly higher propagation rates and frequencies. Studies of candidate mechanisms excluded changes in neuronal excitability, presynaptic release, and GABA receptors but left open a possible contribution of N-methyl-d-aspartate (NMDA) receptor inhibition. These results suggest the extracellular accumulation of synaptically released Zn(2+) can serve as an intrinsic inhibitor to limit SD events. The inhibitory action of extracellular Zn(2+) on SD may counteract to some extent the neurotoxic effects of intracellular Zn(2+) accumulation in acute brain injury models.
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.