FRUCTOSE-1,6-BISPHOSPHATE REDUCES INFARCT VOLUME AFTER REVERSIBLE MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS

Background and Purpose: We tested the hypothesis that fructose-1,6-bisphosphate, when administered 10 minutes before the end of 2 hours of reversible middle cerebral artery occlusion, reduces ischemia-reperfusion injury and infarct volume measured after a 3-day survival period in rats. Methods: After 1 hour and 50 minutes of middle cerebral artery occlusion by the intraluminal suture method, fructose-1,6-bisphosphate, 500 mg/kg in group 1 and 350 mg/kg in group 2 (or an equivalent volume of 1.8% saline as placebo in each group), was given intravenously for a period of 15 minutes to fasted adult Sprague-Dawley rats. After 2 hours of ischemia, the suture was withdrawn and the rats allowed to survive for 3 days. The areas of infarction in 10 hematoxylin-eosin-stained coronal sections of the brain were measured and used to calculate infarct volume. Results: In group 1, fructose-1,6-bisphosphate decreased total cerebral hemispheric infarct volume by 43% (from 199.6+/-11.2 to 114.2+/-35.8 mm3, P<.04; mean+/-SEM). Cerebral cortical and subcortical infarct volumes were decreased by 46% (from 137.3+/-7.5 to 74.1+/-28.6 mm3, p<.04) and 36% (from 62.3+/-5.1 to 40.0+/-8.3 mm3, P<.04), respectively. In group 2, fructose-1,6-bisphosphate had no effect on infarct volume in rats that developed mild intraischemic hyperthermia, but in rats kept normothermic during ischemia, fructose-1,6-bisphosphate reduced subcortical infarct volume from 53.7+/-8.1 to 18.4+/-8.0 mm3 (P<.03). Conclusions: Fructose-1,6-bisphosphate improves functional neurological outcome and reduces infarct volume after reversible middle cerebral artery occlusion in rats.