Intravenous Basic Fibroblast Growth Factor Decreases Brain Injury Resulting From Focal Ischemia in Cats

Abstract

Background and Purpose We tested the hypothesis that intravenous administration of basic fibroblast growth factor (bFGF) during 4 hours of permanent focal ischemia would affect acute brain injury. Methods Halothane-anesthetized cats underwent left middle cerebral artery (MCA) occlusion for 4 hours. Control cats received diluent (n=14). Experimental cats were treated with bFGF at a rate of 5 (n=13), 50 (n=13), or 250 μg/kg per hour (n=9) intravenously beginning 60 minutes after initiation of ischemia and continuing until the end of the protocol. Results As measured by the microsphere method, blood flow to ipsilateral caudate nucleus and ipsilateral inferior temporal cortex was decreased similarly during ischemia, before drug administration, in all groups. Likewise, there was no difference in blood flow to ipsilateral caudate nucleus or inferior temporal cortex as a result of bFGF administration during MCA occlusion. Triphenyltetrazolium-determined injury volume of the ipsilateral cerebral cortex (control, 40±7%; bFGF 5 μg/kg per hour, 22±5%; bFGF 50 μg/kg per hour, 26±7%; bFGF 255 μg/kg per hour, 23±6% of ipsilateral cerebral cortex; mean±SEM) was less in cats treated with bFGF. There was no difference among groups in injury volume to caudate nucleus (control, 29±8%; bFGF 5 μg/kg per hour, 29±8%; bFGF 50 μg/kg per hour, 21±7%; bFGF 250 μg/kg per hour, 32±7% of ipsilateral caudate nucleus). Somatosensory evoked potential amplitude decreased similarly (to <20% of baseline amplitude in all groups) during MCA occlusion and was not altered by bFGF administration. Conclusions These data indicate that systemic administration of bFGF ameliorates acute injury in the cerebral cortex without increasing blood flow during focal ischemia in cats. Because bFGF afforded protection when administered after the onset of ischemia, bFGF may provide its beneficial effect by limiting progression of injury in ischemic border regions.