[Glutamate hypothesis of stroke].
Neuronal injury following focal cerebral ischemia is widely attributed to the excitatory effects of glutamate. However, critical analysis of published data on glutamate toxicity in vitro and the comparison of this data with in vivo release of glutamate and the therapeutic effect of glutamate antagonists raises doubts about a neurotoxic mechanism. An alternative explanation for glutamate-mediated injury is energy failure due to peri-infarct spreading depression-like depolarizations. These depolarizations cause a sharp increase in metabolic activity and therefore produce a mismatch between blood flow and the oxygen requirements of the tissue. The generation of peri-infarct spreading depressions and the associated metabolic workload can be suppressed by glutamate antagonists. As a result, energy failure is also prevented, and the volume of ischemic infarct decreases. Interventions to improve ischemic resistance should therefore aim at improving the oxygen supply or reducing the metabolic workload, rather than interfering with the consequences of a putative excitotoxic injury cascade.
Hossmann
K-A
KA
Max-Planck-Institut für Neurologische Forschung, Abteilung für Experimentelle Neurologie, Köln-Lindenthal, Cologne. hossmann@mpinkoeln.mpg.de
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D002544:Cerebral Infarction / Q000503:physiopathology; D004569:Electroencephalography; D004734:Energy Metabolism / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology* / Q000633:toxicity; D006801:Humans; D020521:Stroke / Q000209:etiology* / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid