Although considerable evidence supports a role for
excitatory amino acids in the pathogenesis of ischemic neuronal injury, few in vivo studies have examined the effect of increasing durations of
ischemia on the extracellular concentrations of these agents. Recently, other
neurotransmitters (e.g.,
glycine and
dopamine) have been implicated in the mechanism of ischemic neuronal injury. Accordingly, this study was undertaken to examine the patterns of changes of extracellular
glutamate,
aspartate,
glycine concentrations in the hippocampus, and
dopamine,
serotonin, and
dopamine metabolites in the caudate nucleus with varying durations (5, 10, or 15 minutes) of transient global
cerebral ischemia as evidence to support their pathogenetic roles. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period.
Glutamate and
aspartate concentrations in the
dialysate increased from baseline by 1-, 5-, and 13-fold and by 4-, 9-, and 31-fold, respectively, for the three ischemic durations. The concentrations returned to baseline rapidly after reperfusion. The peak concentrations of
glutamate and
aspartate were significantly higher with increasing ischemic duration.
Dopamine concentrations increased by approximately 700-fold in response to all three ischemic durations and returned to baseline within 10 min of reperfusion.
Glycine, in contrast, increased during
ischemia by a mean of 4-fold, but remained elevated throughout the 80-min period of reperfusion. The final concentrations of
glycine were significantly higher than baseline levels (p = 0.0002, Mann-Whitney test). That
glutamate and
aspartate concentrations in the hippocampus co-vary with the duration of global
ischemia is taken as supportive evidence of their pathogenetic role in ischemic neuronal injury.(ABSTRACT TRUNCATED AT 250 WORDS)