Fructose-1,6-bisphosphate reduces infarct volume after reversible middle cerebral artery occlusion in rats.
OBJECTIVE
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 After 2 hours of ischemia, the suture was withdrawn and the rats allowed to survive for 3 days.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.
Department of Pediatrics, University of Miami, School of Medicine, FL 33101.
J W
JW
Kuluz
G A
GA
Gregory
Y
Y
Han
W D
WD
Dietrich
C L
CL
Schleien
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002544:Cerebral Infarction / Q000097:blood / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005635:Fructosediphosphates / Q000008:administration & dosage / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D002546:Ischemic Attack, Transient / Q000097:blood / Q000503:physiopathology*; D007773:Lactates / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D001786:Blood Glucose; D005635:Fructosediphosphates; D007773:Lactates; D002245:Carbon Dioxide; C029063:fructose-1,6-diphosphate; D010100:Oxygen