Hydroxyl radical formation in hyperglycemic rats during middle cerebral artery occlusion/reperfusion.
Preexisting hyperglycemia is associated with enhanced reperfusion injury in the postischemic rat brain. The goal of this study was to evaluate whether the hyperglycemic exacerbation of brain injury is associated with enhanced generation of hydroxyl radicals in rats subjected to middle cerebral artery occlusion (2 h), followed by reperfusion (2 h). Magnetic resonance images revealed the exacerbation of focal brain injury in hyperglycemic rats. The salicylate trapping method was used in conjunction with microdialysis to continuously estimate hydroxyl radical production by measurement of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA) during ischemia/reperfusion. In normoglycemic rats, 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 reperfusion), 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 cerebrovascular injury after focal ischemia/reperfusion in hyperglycemic rats.
Wei
J
J
Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555, USA.
Huang
N C
NC
Quast
M J
MJ
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000378:metabolism*; D002536:Cerebral Arteries / Q000378:metabolism*; D002544:Cerebral Infarction / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005841:Gentisates; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
D004791:Enzyme Inhibitors; D005841:Gentisates; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; C010925:2,5-dihydroxybenzoic acid