Mechanisms of cerebral ischemia: intracellular cascades and therapeutic interventions.
In order to gain insight into the pathophysiology of cerebral ischemia, the focus is on the discrete compartmentalization of neurons and the exquisite homeostasis of the neurochemical, ionic, and molecular environment within these compartments. This review looks at excitotoxic mechanisms of cerebral ischemia spatially by separating presynaptic and postsynaptic events as well as temporally by separating early and late events. Drugs that target these events in the excitotoxic cascade are presented and discussed as potential therapeutic interventions for cerebral ischemia. Despite a better understanding of the mechanisms of cerebral ischemia through a myriad of animal model studies with various "neuroprotective" compounds, the challenge remains to apply this knowledge to the development of compounds that demonstrate neuroprotective efficacy in terms of quality-of-life outcomes in humans.
Small
D L
DL
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Canada.
Buchan
A M
AM
D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000209:etiology* / Q000628:therapy; D015220:Calcium Channels / Q000502:physiology; D005609:Free Radicals; D006801:Humans; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
D015220:Calcium Channels; D005609:Free Radicals; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate