Novel concepts in excitotoxic neurodegeneration after stroke.
Brain injury following cerebral ischaemia (stroke) involves a complex combination of pathological processes, including excitotoxicity and inflammation leading to necrotic and apoptotic forms of cell death. At the cellular level, excitotoxicity is mediated by glutamate and its cognate receptors, resulting in increased intracellular calcium and free radical production, and eventual cell death. Recent evidence suggests that scaffolding molecules that associate with glutamate receptors at the postsynaptic density allow coupling of receptor activity to specific second messengers capable of mediating excitotoxicity. These findings have important implications in the search for effective neuroprotective therapies in treating stroke.
Division of Cellular and Molecular Biology, Toronto Western Research Institute, Toronto Western Hospital, Suite 4W-435, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada. maarts@uhnres.utoronto.ca
Michelle M
MM
Aarts
Mark
M
Arundine
Michael
M
Tymianski
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects; D018846:Excitatory Amino Acids / Q000633:toxicity; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism; D008954:Models, Biological; D009410:Nerve Degeneration / Q000139:chemically induced / Q000209:etiology*; D009498:Neurotoxins / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism / Q000502:physiology; D020521:Stroke / Q000150:complications* / Q000209:etiology; D013569:Synapses / Q000378:metabolism
D018846:Excitatory Amino Acids; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate; D002118:Calcium