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A role for tumor necrosis factor-α in ischemia and ischemic preconditioning

During cerebral ischemia, elevation of TNF-α and glutamate to pathophysiological levels may induce dysregulation of normal synaptic processes, leading ultimately to cell death. Previous studies have shown that patients subjected to a mild transient ischemic attack within a critical time window prior...

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Autores principales: Watters, Orla, O'Connor, John J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161872/
https://www.ncbi.nlm.nih.gov/pubmed/21810263
http://dx.doi.org/10.1186/1742-2094-8-87
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author Watters, Orla
O'Connor, John J
author_facet Watters, Orla
O'Connor, John J
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description During cerebral ischemia, elevation of TNF-α and glutamate to pathophysiological levels may induce dysregulation of normal synaptic processes, leading ultimately to cell death. Previous studies have shown that patients subjected to a mild transient ischemic attack within a critical time window prior to a more severe ischemic episode may show attenuation in the clinical severity of the stroke and result in a more positive functional outcome. Studies with organotypic hippocampal cultures and mixed primary hippocampal cultures have shown that prior incubation with low concentrations of glutamate and TNF-α increase the resistance of neurones to a subsequent insult from glutamate, AMPA and NMDA, while co-exposure of TNF-α and for example AMPA may have neuroprotective effects compared to cultures exposed to excitotoxic agents alone. In addition our work has shown that although glutamate and TNF-α pretreatment induces analogous levels of desensitisation of the intracellular calcium dynamics of neurons under resting conditions and in response to acute glutamate stimulation, their downstream signalling pathways involved in this response do not converge. Glutamate and TNF-α would appear to have opposing effects on resting Ca(2+ )levels which supports the proposal that they have distinct modes of preconditioning.
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spelling pubmed-31618722011-08-26 A role for tumor necrosis factor-α in ischemia and ischemic preconditioning Watters, Orla O'Connor, John J J Neuroinflammation Review During cerebral ischemia, elevation of TNF-α and glutamate to pathophysiological levels may induce dysregulation of normal synaptic processes, leading ultimately to cell death. Previous studies have shown that patients subjected to a mild transient ischemic attack within a critical time window prior to a more severe ischemic episode may show attenuation in the clinical severity of the stroke and result in a more positive functional outcome. Studies with organotypic hippocampal cultures and mixed primary hippocampal cultures have shown that prior incubation with low concentrations of glutamate and TNF-α increase the resistance of neurones to a subsequent insult from glutamate, AMPA and NMDA, while co-exposure of TNF-α and for example AMPA may have neuroprotective effects compared to cultures exposed to excitotoxic agents alone. In addition our work has shown that although glutamate and TNF-α pretreatment induces analogous levels of desensitisation of the intracellular calcium dynamics of neurons under resting conditions and in response to acute glutamate stimulation, their downstream signalling pathways involved in this response do not converge. Glutamate and TNF-α would appear to have opposing effects on resting Ca(2+ )levels which supports the proposal that they have distinct modes of preconditioning. BioMed Central 2011-08-02 /pmc/articles/PMC3161872/ /pubmed/21810263 http://dx.doi.org/10.1186/1742-2094-8-87 Text en Copyright ©2011 Watters and O'Connor; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Watters, Orla
O'Connor, John J
A role for tumor necrosis factor-α in ischemia and ischemic preconditioning
title A role for tumor necrosis factor-α in ischemia and ischemic preconditioning
title_full A role for tumor necrosis factor-α in ischemia and ischemic preconditioning
title_fullStr A role for tumor necrosis factor-α in ischemia and ischemic preconditioning
title_full_unstemmed A role for tumor necrosis factor-α in ischemia and ischemic preconditioning
title_short A role for tumor necrosis factor-α in ischemia and ischemic preconditioning
title_sort role for tumor necrosis factor-α in ischemia and ischemic preconditioning
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161872/
https://www.ncbi.nlm.nih.gov/pubmed/21810263
http://dx.doi.org/10.1186/1742-2094-8-87
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