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A role for tumor necrosis factor-alpha in ischemia and ischemic preconditioning
Author(s)
Date Issued
2011-08-02
Date Available
2015-04-10T10:26:16Z
Abstract
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 Ca2+ levels which supports the proposal that they have distinct modes of preconditioning
Sponsorship
Science Foundation Ireland
University College Dublin
Type of Material
Journal Article
Publisher
BioMed Central
Journal
Journal of Neuroinflammation
Volume
8
Start Page
87
End Page
98
Copyright (Published Version)
2011 the Authors
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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