Kainic acid causes redox changes in cerebral cortex extracellular fluid: NMDA receptor activity increases ascorbic acid whereas seizure activity increases uric acid.
Kainic acid (KA) causes seizures and extensive brain damage in rats. To study the effects of KA on the redox state in cerebral cortex extracellular fluid (ECF), ascorbic and uric acid concentrations were measured in intracerebral microdialysis samples before and after systemic KA administration (ip). During seizures, concentrations of ascorbic and uric acid increased 500 and 100%, respectively. When midazolam was given with KA to prevent seizures, ascorbic acid still increased 400%, but uric acid increased only transiently. When the NMDA receptor antagonist aminophosphonovaleric acid (APV) was included in the microdialysis perfusion media, ascorbic acid levels decreased during baseline perfusion in a concentration-dependent manner. APV then suppressed the KA-induced increase in ascorbic acid levels, without blocking seizure activity. In summary, increased uric acid levels in brain ECF activity after KA administration are related to the induced seizure, but ascorbic acid levels are associated with NMDA receptor activity.
Department of Psychiatry and Behavioral Sciences, University of Washington Medical Center, Seattle, USA.
M E
ME
Layton
F E
FE
Samson
T L
TL
Pazdernik
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D008874:Midazolam / Q000494:pharmacology / Q000627:therapeutic use; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism*
D000975:Antioxidants; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D014527:Uric Acid; D001205:Ascorbic Acid; D008874:Midazolam; D007608:Kainic Acid