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The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization

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 elucid...

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Autores principales: Hübel, Niklas, Hosseini-Zare, Mahshid S., Žiburkus, Jokūbas, Ullah, Ghanim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655358/
https://www.ncbi.nlm.nih.gov/pubmed/29023523
http://dx.doi.org/10.1371/journal.pcbi.1005804
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author Hübel, Niklas
Hosseini-Zare, Mahshid S.
Žiburkus, Jokūbas
Ullah, Ghanim
author_facet Hübel, Niklas
Hosseini-Zare, Mahshid S.
Žiburkus, Jokūbas
Ullah, Ghanim
author_sort Hübel, Niklas
collection PubMed
description 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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spelling pubmed-56553582017-11-09 The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization Hübel, Niklas Hosseini-Zare, Mahshid S. Žiburkus, Jokūbas Ullah, Ghanim PLoS Comput Biol Research Article 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. Public Library of Science 2017-10-12 /pmc/articles/PMC5655358/ /pubmed/29023523 http://dx.doi.org/10.1371/journal.pcbi.1005804 Text en © 2017 Hübel et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hübel, Niklas
Hosseini-Zare, Mahshid S.
Žiburkus, Jokūbas
Ullah, Ghanim
The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization
title The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization
title_full The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization
title_fullStr The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization
title_full_unstemmed The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization
title_short The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization
title_sort role of glutamate in neuronal ion homeostasis: a case study of spreading depolarization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655358/
https://www.ncbi.nlm.nih.gov/pubmed/29023523
http://dx.doi.org/10.1371/journal.pcbi.1005804
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