Elevation of neuroactive substances in the cortex of cats during prolonged focal ischemia.
Sustained accumulation of excitatory amino acids and other neuroactive substances may contribute to the delayed progression of infarction in focal ischemia. Following occlusion of the left middle cerebral artery (MCAO), extracellular amino acid and purine catabolite concentrations as well as local CBF were repeatedly monitored for up to 15 h in auditory (A) and somatosensory (SF) cortices of seven halothane-anesthetized cats using microdialysis/HPLC and hydrogen clearance. MCAO resulted in persistent reduction of local CBF, which was more severe in A (n = 6) than in SF (n = 6). Accordingly, higher transmitter amino acid and purine catabolite concentrations were found in A than in SF during ischemia. Aspartate, glutamate, and gamma-aminobutyrate (GABA) as well as hypoxanthine and inosine reached maximum levels 1-2 h after onset of ischemia (15-, 7-, 31-, 8-, and 14-fold increases, respectively). Maximum levels remained almost constant, with the exception of inosine, which decreased subsequently. Glycine seemed to increase with prolonged ischemia and reached maximum levels (10-fold) 15 h after occlusion. Adenosine peaked 30 min after occlusion (54-fold) and decreased thereafter to control levels within 1-2 h. One hour after occlusion, CBF thresholds for amino acid elevation were lower (glutamate and GABA approximately 20 ml 100 g-1 min-1 and glycine approximately 10 ml 100 g-1 min-1) than 6 and 15 h after occlusion (thresholds for all amino acids at approximately 30 ml 100 g-1 min-1). These results indicate that in prolonged ischemia, excitotoxicity is an important factor, particularly in border zones of ischemic foci.(ABSTRACT TRUNCATED AT 250 WORDS)
Matsumoto
K
K
Max-Planck-Institut für Neurologische Forschung, Köln, Germany.
Graf
R
R
Rosner
G
G
Taguchi
J
J
Heiss
W D
WD
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002415:Cats; D002540:Cerebral Cortex / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D003956:Dialysis; D005260:Female; D008297:Male; D009498:Neurotoxins / Q000378:metabolism*; D009994:Osmolar Concentration; D011687:Purines / Q000378:metabolism*; D013997:Time Factors
D000596:Amino Acids; D009498:Neurotoxins; D011687:Purines