Differences in ischemia-induced accumulation of amino acids in the cat cortex.
It is well established that excitatory amino acid neurotransmitters are extensively liberated during ischemia and that they have neurotoxic properties contributing to neuronal injury. To study changes in the liberation of excitatory and other amino acids during cerebral ischemia, we measured their extracellular concentrations and related them to blood flow levels and electrophysiologic activity (electrocorticogram and auditory evoked potentials) before and for up to 2 hours after multiple cerebral vessel occlusion in 14 anesthetized cats. Blood flow levels between 0 and 43 ml/100 g/min were reached. Concentrations of the excitatory amino acid neurotransmitters increased most (aspartate 10-fold, glutamate 30-fold, and gamma-aminobutyric acid 300-fold compared with control values) below a blood flow threshold of 20 ml/100 g/min. The total power of the electrocorticogram and the amplitude of the auditory evoked potentials were affected below the same blood flow threshold. In contrast, concentrations of the nontransmitter amino acids taurine, alanine, asparagine, serine, and glutamine increased 1.5-5-fold as blood flow decreased, while concentrations of the essential amino acids phenylalanine, valine, leucine, and isoleucine did not change during cerebral ischemia. The great increases in concentrations of the excitatory amino acid neurotransmitters below a blood flow threshold close to that for functional disturbance is in accordance with the role of these amino acids in ischemic cell damage. Their release at blood flow levels compatible with cell survival and the increase in their concentrations with severity and duration of cerebral ischemia imply that excitotoxic antagonists may have potential as therapeutic agents.
Shimada
N
N
Max-Planck-Institut für neurologische Forschung, Köln, F.R.G.
Graf
R
R
Rosner
G
G
Heiss
W D
WD
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism / Q000503:physiopathology; D002415:Cats; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D005072:Evoked Potentials, Auditory; D005260:Female; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*
D000596:Amino Acids; D018377:Neurotransmitter Agents