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Cellular and Molecular Life Sciences CMLS

, Volume 61, Issue 6, pp 657–668 | Cite as

Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury

  • M. Arundine
  • M. TymianskiEmail author
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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.

Glutamate NMDA receptor calcium nitric oxide ROS ischemia traumatic brain injury postsynaptic density protein-95 superoxide 

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Copyright information

© Birkhäuser-Verlag Basel 2004

Authors and Affiliations

  1. 1.Toronto Western Hospital Research InstituteTorontoCanada
  2. 2.Department of PhysiologyUniversity of TorontoTorontoCanada

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