NEUROPROTECTIVE ACTIVITY OF FRUCTOSE-1,6-BISPHOSPHATE FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA IN THE MONGOLIAN GERBIL

We examined the protective activity of fructose-1,6-bisphosphate (FBP) on mortality and delayed hippocampal cell death induced by transient cerebral ischemia in the Mongolian gerbil. Forebrain ischemia was prod uced by bilaterally occluding the common carotid arteries for 15 min u sing microaneurysm clips; then the blood supply to the brain was resto red. The number of survivors was counted for 8 days, and the histopath ological damage in the CA1 region of the hippocampus was scored accord ing to the semiquantitative scale of Rudolphi and colleagues. When inj ected 15 min before the ischemic insult, FBP (100 and 333 mg/kg, i.v.) significantly reduced the rate of mortality during the 8-day observat ion period. Equivalent doses of fructose and fructose monophosphate di d not improve survival, and neither did low doses (33 mg/kg) of FBP. F BP also produced a significant degree of protection against the CA1 py ramidal cell loss in comparison with its vehicle (distilled water). Co nversely, when we administered the compound, at the same dose, 15 min after the release of the arterial occlusion, we observed neither a sig nificant reduction of mortality nor significant protection against hip pocampal CA1 pyramidal cell loss. These results suggest that FBP posse sses salutary properties against the damages induced by transient cere bral ischemia, although they are evident only when the compound is adm inistered before the resolution of the ischemic injury.