ArticleThe Journal of physiology2012
Sustained NMDA receptor activation by spreading depolarizations can initiate excitotoxic injury in metabolically compromised neurons.
Article in The Journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 80 citations in OpenAlex.
- Local targeted suppression of neocortical spreading depolarization amplitude by viral expression of KCa3.1 channels.Gene therapy · 2026Article
- 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
- Initiation site of experimentally-evoked spreading depolarizations influence tissue outcomes in a murine stroke model.Experimental neurology · 2026Article
- Review
- The metabolic consequences of evoked spreading depolarization in brain slices.Scientific reports · 2026Article
- Initiation site of experimentally-evoked spreading depolarizations influence tissue outcomes in a murine stroke model.bioRxiv : the preprint server for biology · 2025Article
- Spreading depolarizations exhaust neuronal ATP in a model of cerebral ischemia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Contralesional hippocampal spreading depolarization promotes functional recovery after stroke.Nature communications · 2025Article
- 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
- Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura.Biomolecules · 2024Article
- Spreading Depolarization Induces a Transient Potentiation of Excitatory Synaptic Transmission.Neuroscience · 2024Article
- Beyond nimodipine: advanced neuroprotection strategies for aneurysmal subarachnoid hemorrhage vasospasm and delayed cerebral ischemia.Neurosurgical review · 2024Review
- Trauma in Neonatal Acute Brain Slices Alters Calcium and Network Dynamics and Causes Calpain-Mediated Cell Death.eNeuro · 2024Article
- 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
- Ketamine improves neuronal recovery following spreading depolarization in peri-infarct tissues.Journal of neurochemistry · 2024Article
- Spreading depolarizations pose critical energy challenges in acute brain injury.Journal of neurochemistry · 2024Review
- 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
- Plasticity of perisynaptic astroglia during ischemia-induced spreading depolarization.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Spreading depolarizations (SDs) are slowly propagating waves of near-complete neuronal and glial depolarization. SDs have been recorded in patients with brain injury, and the incidence of SD significantly correlates with outcome severity. Although it is well accepted that the ionic dyshomeostasis of SD presents a severe metabolic burden, there is currently limited understanding of SD-induced injury processes at a cellular level. In the current study we characterized events accompanying SD in the hippocampal CA1 region of murine brain slices, using whole-cell recordings and single-cell Ca(2+) imaging. We identified an excitatory phase that persisted for approximately 2 min following SD onset, and accompanied with delayed dendritic ionic dyshomeostasis. The excitatory phase coincided with a significant increase in presynaptic glutamate release, evidenced by a transient increase in spontaneous EPSC frequency and paired-pulse depression of evoked EPSCs. Activation of NMDA receptors (NMDARs) during this late excitatory phase contributed to the duration of individual neuronal depolarizations and delayed recovery of extracellular slow potential changes. Selectively targeting the NMDAR activation following SD onset (by delayed pressure application of a competitive NMDAR antagonist) significantly decreased the duration of cellular depolarizations. Recovery of dendritic Ca(2+) elevations following SD were also sensitive to delayed NMDA antagonist application. Partial inhibition of neuronal energy metabolism converted SD into an irrecoverable event with persistent Ca(2+) overload and membrane compromise. Delayed NMDAR block was sufficient to prevent these acute injurious events in metabolically compromised neurons. These results identify a significant contribution of a late component of SD that could underlie neuronal injury in pathological circumstances.
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