Comparative Effect of Transient Global Ischemia on Extracellular Levels of Glutamate, Glycine, and γ‐Aminobutyric Acid in Vulnerable and Nonvulnerable Brain Regions in the Rat

Mordecai Y.‐T Globus, Raul Busto, Elena Martinez, Isabel Valdés, W. Dalton Dietrich, Myron D. Ginsberg

Research output: Contribution to journalArticlepeer-review

262 Scopus citations

Abstract

We evaluated whether regional differences in the magnitude of glutamate, γ-aminobutyric acid (GABA), and glycine release could explain why some regions are vulnerable to ischemia whereas others are spared. By means of the microdialysis technique, the temporal profile of ischemia-induced changes in extracellular levels of glutamate, GABA, and glycine was compared in regions that demonstrate differing susceptibilities to a 10- and 20-min ischemic insult (dorsal hippocampus, anterior thalamus, somatosensory cortex, and dorsolateral striatum). The degree of ischemia (as established by local cerebral blood flow reduction) and the magnitude of histopathological neuronal damage were also evaluated in these regions. The blood flow reduction was severe and uniform in all regions; however, the histopathological outcome illustrated a different pattern. Whereas the CA1 sector of the hippocampus was severely damaged, the thalamus and cortex were relatively spared from both 10 and 20 min of ischemia. Striatal neurons were resistant to a 10-min insult but severely damaged after 20 min of ischemia. Ischemia-induced increases in glutamate and GABA content were of a similar magnitude and temporal profile in all four brain regions. A uniform increase in extracellular glycine levels was also observed in all four brain structures. The postischemic response, however, was different. Glycine levels remained twofold higher than baseline in the hippocampus but fell to baseline in the cortex and thalamus after both 10- and 20-min insults. In the striatum, glycine levels returned to baseline after 10 min of ischemia but remained relatively high after a 20-min insult. Although ischemic neuronal damage was not related to glutamate release, it correlated with the "excitotoxic index," whose value was derived from the following equation: [glutamate] X [glycine]/[GABA]. No significant changes were observed in the excitotoxic index during ischemia. However, a significant increase in the index was observed in vulnerable brain regions during the early and late recirculation periods. These results suggest that the imbalance between excitation and inhibition, reflected by changes in the excitotoxic index, may account for regional vulnerability to ischemia.

Original languageEnglish (US)
Pages (from-to)470-478
Number of pages9
JournalJournal of neurochemistry
Volume57
Issue number2
DOIs
StatePublished - Aug 1991

Keywords

  • γ-Aminobutyric acid
  • Excitotoxicity
  • Global cerebral ischemia
  • Glutamate
  • Glycine
  • Microdialysis
  • Selective vulnerability

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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