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Hyperbaric Oxygenation Treatment during Ischemia Alleviates Brain Injury and Reduces Striatal Hydroxyl Free Radicals Formation and Glutamate Release
Zhong-jin Yang, M.D., Micheal Tucci, M.D., Yan Xie, M.D., Gary Wang, Ph.D., M.D., Enrico M. Camporesi, M.D.
Anesthesiology, Upstate Medical University, Syracuse, New York, United States.
Numerous studies have shown that oxygen free radicals (OFR) and glutamate, when present in excessive amounts extracellularly, are neurotoxic and play an important role in the development of ischemia-reperfusion brain injury. Hydroxyl free radicals are the most reactive and hazardous OFR. A linkage between increased glutamate release and enhanced OFR generation has been suggested. We previously showed that hyperbaric oxygen (HBO2) alleviated focal ischemia-reperfusion brain injury. We hypothesized that the alleviation of focal brain injury by HBO2 may be associated with decreased OFR formation and glutamate release. In vivo microdialysis was used in the present study to examine the effect of HBO2 on 1)hydroxyl free radicals: 2,5-dihydroxybenzoic acid (2,5-DHBA) and 2,3-dihydroxybenzoic acid (2,3-DHBA) formation, the product of salicylate trapping of hydroxyl free radicals; and 2) glutamate level in the striatum during ischemia and reperfusion. Focal cerebral ischemia was induced with the middle cerebral artery occlusion (MCAO). Control rats (n=8) were subjected to one-hour ischemia. Study rats (n=8) were treated with HBO2 (2.8 ATA, 100% O2) during one-hour ischemia and then returned to room air during 2 h reperfusion. Ringer's solution containing 2 mmol/L sodium salicylate was perfused at 1µl/min. The samples were continuously collected and 2,5-DHBA and 2,3-DHBA were measured by HPLC immediately at 15-minute intervals. Glutamate was analyzed using CMA 600 analyzer. The infarct size was determined by 2% 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) stain. Results were considered significantly different at a values of p< 0.05.

Infarct size was significantly less in HBO2 group than in Control group, being 7.5±3.0 and 27.0± 6.0, respectively. There were no differences in the baseline levels of 2,5-DHBA, 2,3-DHBA and glutamate between two groups. Occlusion of MCA induced significant increase in the levels of 2,5-DHBA and 2,3-DHBA and reached a peak at 45 min, being approximately 2-fold and 4-fold of baseline levels respectively; and maintained at elevated levels during reperfusion. The level of glutamate increased approximately 2 times at 30 min ischemia and continued to increase and reached approximately 10 times of baseline level during reperfusion. In the HBO2 treated rats, there was no significant changes in either 2,5-DHBA, 2,3-DHBA or glutamate levels in comparison with baseline or Controls.

This study shows that HBO2, when administered during ischemia, offers significant neuroprotection in this experimental transient focal cerebral ischemia-reperfusion rat model. Reduced formation of hydroxyl free radicals and decreased glutamate release might contribute to the protective effect of HBO2 in brain ischemia-reperfusion injury.

Anesthesiology 2003; 99: A839