Simultaneous measurement of salicylate hydroxylation and glutamate release in the penumbral cortex following transient middle cerebral artery occlusion in rats.
Using the microdialysis technique and laser-Doppler flowmetry, we performed simultaneous measurement of salicylate hydroxylation and glutamate release along with local CBF in the ischemic penumbral cortex of rat brain subjected to normothermic transient middle cerebral artery (MCA) occlusion. Cortical CBF fell to 24 +/- 11% (mean +/- SD) during ischemia and recovered to 84 +/- 16% during reperfusion. Extracellular glutamate levels increased by 6.5-fold above baseline 10 min following MCA occlusion but subsequently returned to near baseline levels in spite of the persistent ischemia. Increase in 2,3- and 2,5-dihydroxybenzoic acid (DHBA) concentrations in the microdialysis perfusate was confirmed during both ischemia and reperfusion phase. Although the temporal profile and amount of salicylate hydroxylation were heterogeneous among individual animals, integrated 2,3-DHBA concentrations during reperfusion were correlated positively with integrated glutamate concentrations during ischemia and negatively with mean postischemic CBF. These relationships suggest a possible association of the enhanced production of 2,3-DHBA during reperfusion with larger amounts of intraischemic glutamate release and lower levels of post-ischemic CBF.
Department of Neurology, University of Miami School of Medicine, Florida 33101, USA.
T
T
Morimoto
M Y
MY
Globus
R
R
Busto
E
E
Martinez
M D
MD
Ginsberg
D000137:Acid-Base Imbalance / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D002851:Chromatography, High Pressure Liquid; D016166:Free Radical Scavengers / Q000378:metabolism*; D005841:Gentisates; D018698:Glutamic Acid / Q000378:metabolism*; D062385:Hydroxybenzoates / Q000032:analysis; D006900:Hydroxylation; D007502:Iron Chelating Agents / Q000032:analysis; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D012459:Salicylates / Q000378:metabolism*; D020156:Salicylic Acid
D016166:Free Radical Scavengers; D005841:Gentisates; D062385:Hydroxybenzoates; D007502:Iron Chelating Agents; D012459:Salicylates; D018698:Glutamic Acid; C009135:2,3-dihydroxybenzoic acid; D020156:Salicylic Acid; C010925:2,5-dihydroxybenzoic acid