Delayed intravenous administration of basic fibroblast growth factor (bFGF) reduces infarct volume in a model of focal cerebral ischemia/reperfusion in the rat

Basic fibroblast growth factor (bFGF) is a potent neurotrophic and vasoactive peptide. Previous studies have shown that intraventricularly-administered bFGF reduces the size of cerebral infarcts following focal ischemia. In the current study, we tested the effects of intravenously-administered bFGF in a model of focal ischemia/reperfusion. The right middle cerebral artery of mature male Wistar rats was occluded by intraluminal suture. After 2 h of occlusion, the suture was removed and intravenous infusion of bFGF in vehicle (45 mu g/kg/h) or vehicle alone was begun, lasting 3 h. Animals were weighed and evaluated neurologically until sacrifice 7 days after ischemia. The volume of cerebral infarcts was then determined by H and E staining and image analysis. We found a 40% reduction in infarct volume in bFGF- vs. vehicle-treated rats (n = 11 vs. 11, P < 0.05). Reduction in infarct volume was associated with improved neurological outcome and regained body weight in bFGF-treated animals (both P < 0.05). No change in blood pressure was found during bFGF treatment. These results show that the delayed intravenous administration of bFGF reduces infarct size in this model of focal ischemia/reperfusion. The mechanisms of infarct reduction may include direct cytoprotective and/or vasoactive effects.