Secondary elevation of extracellular neurotransmitter amino acids in the reperfusion phase following focal cerebral ischemia.
The purpose of this study was to evaluate amino acid neurotransmitter dynamics in the reperfusion phase after transient cerebral ischemia. In vivo microdialysis was used to measure extracellular amino acid levels in a rabbit model of focal ischemia. During 30 min of transient ischemia (n = 5), small but significant (p < 0.05) increases in glutamate, aspartate, gamma-aminobutyric acid (GABA), and taurine were noted. These elevations rapidly returned to baseline levels upon recirculation and remained constant for up to 5.5 h of reperfusion. In rabbits subjected to 2 h of transient ischemia (n = 5), two phases of amino acid release were seen. During ischemia, large (5- to 50-fold) elevations in glutamate, aspartate, GABA, and taurine occurred, as expected. These elevations rapidly normalized upon unocclusion. However, significant (p < 0.05) secondary elevations in glutamate, aspartate, and GABA occurred after 2-4 h of reperfusion. Regression analysis demonstrated significant correlations between primary (ischemic) and secondary (reperfusion) efflux. In permanent ischemia (n = 5), amino acid levels remained elevated throughout the entire experiment. Secondary elevations in excitatory amino acids may further contribute to the excitotoxic cascade during reperfusion.
Center for Imaging and Pharmaceutical Research, Harvard Medical School, Massachusetts General Hospital, Boston, USA.
K
K
Matsumoto
E H
EH
Lo
A R
AR
Pierce
E F
EF
Halpern
R
R
Newcomb
D000596:Amino Acids / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001479:Basal Ganglia / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011817:Rabbits; D012044:Regression Analysis; D015427:Reperfusion Injury / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D018377:Neurotransmitter Agents; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid