ArticlePLoS computational biology2017
The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization.
Article in PLoS computational biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Thirty years later: Revisiting the glial failure hypothesis as the homeostatic organizing principle of ischemic injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Computer models predict differential dendritic vulnerability with ischemia and spreading depression.PLoS computational biology · 2026Article
- Neuronal and astrocytic sodium-calcium exchanger differentially regulates calcium and sodium overload during ischemic stroke.JCI insight · 2026Article
- The Role of the Glutamate-Glutamine Cycle in Synaptic Transmission During Ischemia and Recovery.The European journal of neuroscience · 2026Article
- The Role of Loss-of-Function KCNH2 Variants in Cardiac Arrhythmias, Seizures and the Risk of Sudden Unexpected Death in Epilepsy.Journal of neurochemistry · 2026Review
- Computer models predict differential dendritic vulnerability with ischemia and spreading depression.bioRxiv : the preprint server for biology · 2025Article
- Say hello to my little friend… micronutraceuticals in neuroenergetics, neuronal health, and neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Glutamate load fosters spreading depolarization under osmotic stress in brain slices.Frontiers in cellular neuroscience · 2025Article
- A valuation based theory of learning's origin and development.Frontiers in systems neuroscience · 2025Article
- The role of extracellular glutamate homeostasis dysregulated by astrocyte in epileptic discharges: a model evidence.Cognitive neurodynamics · 2024Article
- Astrocytes: new evidence, new models, new roles.Biophysical reviews · 2023Review
- Narrative review of roles of astrocytes in subarachnoid hemorrhage.Annals of translational medicine · 2023Review
- Plasticity of perisynaptic astroglia during ischemia-induced spreading depolarization.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Glioma epileptiform activity and progression are driven by IGSF3-mediated potassium dysregulation.Neuron · 2023Article
- Interneuronal dynamics facilitate the initiation of spike block in cortical microcircuits.Journal of computational neuroscience · 2022Article
- The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention.Neurocritical care · 2022Review
- Classification of bursting patterns: A tale of two ducks.PLoS computational biology · 2022Review
- Perspectives on the basis of seizure-induced respiratory dysfunction.Frontiers in neural circuits · 2022Review
- Article
- An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain.PLoS computational biology · 2021Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Simultaneous changes in ion concentrations, glutamate, and cell volume together with exchange of matter between cell network and vasculature are ubiquitous in numerous brain pathologies. A complete understanding of pathological conditions as well as normal brain function, therefore, hinges on elucidating the molecular and cellular pathways involved in these mostly interdependent variations. In this paper, we develop the first computational framework that combines the Hodgkin-Huxley type spiking dynamics, dynamic ion concentrations and glutamate homeostasis, neuronal and astroglial volume changes, and ion exchange with vasculature into a comprehensive model to elucidate the role of glutamate uptake in the dynamics of spreading depolarization (SD)-the electrophysiological event underlying numerous pathologies including migraine, ischemic stroke, aneurysmal subarachnoid hemorrhage, intracerebral hematoma, and trauma. We are particularly interested in investigating the role of glutamate in the duration and termination of SD caused by K+ perfusion and oxygen-glucose deprivation. Our results demonstrate that glutamate signaling plays a key role in the dynamics of SD, and that impaired glutamate uptake leads to recovery failure of neurons from SD. We confirm predictions from our model experimentally by showing that inhibiting astrocytic glutamate uptake using TFB-TBOA nearly quadruples the duration of SD in layers 2-3 of visual cortical slices from juvenile rats. The model equations are either derived purely from first physical principles of electroneutrality, osmosis, and conservation of particles or a combination of these principles and known physiological facts. Accordingly, we claim that our approach can be used as a future guide to investigate the role of glutamate, ion concentrations, and dynamics cell volume in other brain pathologies and normal brain function.
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