In vivo evidence of hydroxyl radical formation induced by elevation of extracellular glutamate after cerebral ischemia in the cortex of anesthetized rats.

The in vivo interrelation between excitotoxicity and oxidative stress following cerebral ischemia in the cortex of anesthetized rats was investigated. Cerebral ischemia was induced by ligation of the bilateral common carotid arteries and the unilateral middle cerebral artery. Microdialysis perfusion with on-line high-performance liquid chromatography was used to monitor the hydroxyl radical levels. Extracellular hydroxyl radical levels were quantitated as the increased formation of 2.3 and 2.5 dihydroxybenzoic acid (DHBA), the hydroxylative products of salicylic acid contained in the microdialysis perfusion solutions. Elevated cortex extracellular glutamate content, resulting from the cerebral ischemia, caused an increase in the formation of hydroxyl radicals. Exogenous perfusion of authentic glutamate solutions through implanted microdialysis probes also resulted in increased hydroxyl radical formation in the cortex. The 2.3 and 2.5 DHBA levels remained elevated for an entire 80-min ischemic period. These results suggest that, after cerebral ischemia, increased oxidative stress did occur in anesthetized rats, and the oxidative stress may result from increased excitotoxicity.