title: Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury.
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 Ca(2+) 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.
authors.affiliation: Toronto Western Hospital Research Institute, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Arundine
authors.forename: M
authors.initials: M
authors.lastname: Tymianski
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D016202:N-Methylaspartate / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate