title: Elevated extracellular glutamate concentrations increased malondialdehyde production in anesthetized rat brain cortex.
abstract: Oxidative stress is believed to be involved in the damaging mechanism of excitotoxic insult. Thus, we investigated the effect of elevated extracellular glutamate levels on malondialdehyde production, a common index of lipid peroxidation, in anesthetized rat brain cortex. Elevation of extracellular glutamate levels was achieved either by exogenously perfusing glutamate solutions, or by perfusing L-trans-pyrrolidine-2,4-dicarboxylate (PDC), a competitive inhibitor of glutamate uptake transporter, through an implanted microdialysis probe. Malondialdehyde levels in the microdialysates, which were reacted with thiobarbituric acid, were analyzed by a high performance liquid chromatography system equipped with a fluorescence detector. Perfusion of glutamate (1.5 and 15 mM) resulted in dose-dependent increases in extracellular malondialdehyde production (as high as a 6-fold increase in malondialdehyde production following perfusion of 15 mM glutamate solution). PDC (3.14 and 31.4 mM), not only significantly increased the extracellular glutamate levels in a dose-dependent manner, but also dramatically increased malondialdehyde production (as high as 20-fold increase). These results suggest that excitotoxicity induces oxidative stress in anesthetized rat brain cortex, as evidenced by the glutamate-induced increase in malondialdehyde production.
authors.affiliation: Department of Education and Research, Taichung Veterans General Hospital, Taiwan.
authors.forename: C S
authors.initials: CS
authors.lastname: Yang
authors.forename: P J
authors.initials: PJ
authors.lastname: Tsai
authors.forename: N N
authors.initials: NN
authors.lastname: Lin
authors.forename: J S
authors.initials: JS
authors.lastname: Kuo
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D027322:Amino Acid Transport System X-AG; D000758:Anesthesia; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D017551:Microdialysis; D009498:Neurotoxins / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D003998:Dicarboxylic Acids; D009498:Neurotoxins; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D018698:Glutamic Acid; D008315:Malondialdehyde; C083486:pyrrolidine-2,4-dicarboxylic acid