Excitotoxic index--a biochemical marker of selective vulnerability.
We have previously demonstrated that elevated intraischemic glutamate levels are insufficient, of themselves, to engender ischemic damage. Glycine and gamma-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] x [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 less than 0.01, ANOVA) as well as later recirculation times (2 h = 111.3 +/- 30.9 and 20.9 +/- 3.6, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neurology, University of Miami School of Medicine, FL 33101.
M Y
MY
Globus
M D
MD
Ginsberg
R
R
Busto
D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D005998:Glycine / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009498:Neurotoxins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015415:Biomarkers; D005971:Glutamates; D009498:Neurotoxins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine