HYDROXYL RADICAL FORMATION IN HYPERGLYCEMIC RATS DURING MIDDLE CEREBRAL-ARTERY OCCLUSION REPERFUSION/

Preexisting hyperglycemia is associated with enhanced reperfusion inju ry in the postischemic rat brain. The goal of this study was to evalua te whether the hyperglycemic exacerbation of brain injury is associate d with enhanced generation of hydroxyl radicals in rats subjected to m iddle cerebral artery occlusion (2 h), followed by reperfusion (2 h). Magnetic resonance images revealed the exacerbation of focal brain inj ury in hyperglycemic rats. The salicylate trapping method was used in conjunction with microdialysis to continuously estimate hydroxyl radic al production by measurement of the stable adducts 2,3- and 2,5-dihydr oxybenzoic acid (DHBA) during ischemia/reperfusion. In normoglycemic r ats, from a mean baseline level of 130 nmol/l, 2,3-DHBA levels surged to peak levels of 194 nmol/l 45 min into ischemia and to 197 nmol/l 15 -30 min into the reperfusion period, returning to baseline by 2 h into reperfusion. A similar temporal profile was observed in hyperglycemic rats, except that absolute 2,3-DHBA levels were higher(165 nmol/l at baseline, 317 nmol/l peak during ischemia, 333 nmol/l peak during repe rfusion), and levels remained significantly high (p < .05) throughout the reperfusion period. These results suggest that hydroxyl radical is an important contributor to the exacerbation of neuronal and cerebrov ascular injury after focal ischemia/reperfusion in hyperglycemic rats. (C) 1997 Elsevier Science Inc.