Ischemia-induced accumulation of extracellular amino acids in cerebral cortex, white matter, and cerebrospinal fluid.
In a global model of brain ischemia, accumulation of amino acids was studied in the extracellular space of the auditory cortex and the internal capsule using microdialysis, and in CSF of halothane anesthetized cats. In both brain regions, blood flow determined by hydrogen clearance decreased below 10 ml/100 g/min after extracranial multiple-vessel occlusion, and extracellular potassium activity (Ke) measured in the dialysate increased significantly. A delayed rise in Ke was observed in CSF. In contrast, ischemic amino acid accumulation differed markedly between the two brain regions investigated. In cortex, transmitter amino acids glutamate, aspartate, and gamma-aminobutyric acid (GABA) rose almost immediately after onset of ischemia, and increased 30-, 25-, and 250-fold, respectively, after 2 h of ischemia. The nontransmitter amino acids taurine, alanine, and serine increased 10-, seven-, and fourfold, respectively, whereas glutamine and essential amino acids (valine, phenylalanine, isoleucine, and leucine) increased only 1.5-fold. In the internal capsule, increases in amino acids, if any, were delayed and much smaller than in cortex. The largest alteration was a fivefold elevation of GABA. In CSF, changes in amino acids were small and comparable to those in the internal capsule. Our results demonstrate that ischemia-induced extracellular amino acid accumulation is a well localized phenomenon restricted to gray matter structures that possess release and reuptake systems for these substances. We assume that amino acids diffuse slowly into adjacent while matter structures, and into CSF.
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 / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002415:Cats; D002540:Cerebral Cortex / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism
D000596:Amino Acids; D011188:Potassium