Excitotoxic index - a biochemical marker of selective vulnerability

Mordecai Y.T. Globus, Myron D. Ginsberg, Raul Busto

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

We have previously demonstrated that elevated intraischemic glutamate levels are insufficient, of themselves, to engender ischemic damage. Glycine and γ-aminobutyric acid (GABA), which modulate glutamatergic activity, may also play a significant role. We compared ischemia-induced changes in glutamate, glycine, and GABA release in a selectively vulnerable region (dorsolateral striatum) to the changes occurring in a region, although rendered ischemic, is usually spared with 20 min ischemia (anterior thalamus). Regional extracellular neurotransmitter levels were measured by microdialysis before, during, and after 20 min of global ischemia induced by 2-vessel occlusion plus systemic hypotension in the rat (n = 5). Similar ischemia-induced increases in glutamate, GABA, and glycine were observed in both striatum and thalamus (19-25 fold, 43-52 fold, and 3-4 fold, respectively). During recirculation, both glutamate and GABA returned to baseline in both regions by 30 min of reperfusion. Glycine levels remained two-fold higher than baseline in the striatum but fell to baseline in the thalamus. To derive a quantitative descriptor reflecting the composite magnitude of aminoacid neurotransmitter changes with ischemia, we defined the 'excitotoxic index' as: [glutamate] × [glycine]/[GABA]. While increases in the excitotoxic index during ischemia were similar for striatum and thalamus, a marked and highly significant increase was found in the striatum compared to the thalamus at early (1 h = 91.5 ± 27.4 and 25.1 ± 6.3, P < 0.01, ANOVA) as well as later recirculation times (2 h = 111.3 ± 30.9 and 20.9 ± 3.6, P < 0.01). Thus, the excitotoxic index, which reflects the composite neurotransmitter response, appears to be a reliable biochemical marker of selective neuronal vulnerability.

Original languageEnglish (US)
Pages (from-to)39-42
Number of pages4
JournalNeuroscience Letters
Volume127
Issue number1
DOIs
StatePublished - Jun 10 1991

    Fingerprint

Keywords

  • Excitotoxicity
  • GABA
  • Global cerebral ischemia
  • Glutamate
  • Glycine
  • Microdialysis
  • Selective vulnerability

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this