Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury (original) (raw)

Abstract

Stroke and neurotrauma mediate neuronal death through a series of events that involve multiple interdependent molecular pathways. It has been suggested that these pathways are triggered following elevations in extracellular excitatory amino acids, primarily glutamate [1]. This report outlines mechanisms involving glutamate-mediated excitotoxicity with specific focus on (i) the role of Ca2+ in neurotoxicity, (ii) The concept of ‘source specificity’ of neurotoxicity, (iii) the role of the ionotropic N-methyl-D-aspartate (NMDA)-subtype glutamate receptor and its associated submembrane molecules that may give rise to signaling specificity in excitotoxicity and (iv) the role of glutamate-mediated free-radical generation and associated cell death pathways. We also highlight a novel, peptide-based approach for uncoupling NMDA receptors from excitotoxicity in the rat central nervous system subjected to focal ischemia, thereby reducing stroke infarct volume and improving neurological functioning.

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Authors and Affiliations

  1. Toronto Western Hospital Research Institute, 399 Bathurst St., M5T 2S8, Toronto, Ontario, Canada
    M. Arundine & M. Tymianski
  2. Department of Physiology, University of Toronto, M5G 1X8, Toronto, Ontario, Canada
    M. Arundine & M. Tymianski

Authors

  1. M. Arundine
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  2. M. Tymianski
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Corresponding author

Correspondence toM. Tymianski.

Additional information

Received 11 August 2003; received after revision 15 September 2003; accepted 17 September 2003

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Arundine, M., Tymianski, M. Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury.CMLS, Cell. Mol. Life Sci. 61, 657–668 (2004). https://doi.org/10.1007/s00018-003-3319-x

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