EFFECT OF BASIC FIBROBLAST GROWTH-FACTOR ON EXPERIMENTAL FOCAL ISCHEMIA STUDIED BY DIFFUSION-WEIGHTED AND PERFUSION IMAGING

Background and Purpose Basic fibroblast growth factor (bFGF) has docum ented neuroprotective properties. This study was performed to evaluate the effects of bFGF on infarct size when administered 30 minutes afte r induction of focal cerebral ischemia in rats. Diffusion-weighted and perfusion MRI were used during the drug infusion. Methods We blindly randomized 20 Sprague-Dawley rats to receive either drug (n=10) or veh icle (n=10). The animals underwent middle cerebral artery (MCA) occlus ion using the suture model. Diffusion-weighted MRI was initiated 30 mi nutes after induction of ischemia and repeated frequently for 3.5 hour s. Drug (45 mu g/kg per hour) or vehicle (saline) infusion began 30 mi nutes after MCA occlusion and continued for 3 hours. Perfusion images were made at 25, 90, and 150 minutes after MCA occlusion. The animals were killed after 24 hours of permanent MCA occlusion, and brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Results The T TC-derived, corrected infarct volume postmortem in the bFGF-treated gr oup was significantly smaller than that in controls (126.6+/-51.9 vers us 180.2+/-54.9 mm(3), mean+/-SD, P=.038). Diffusion imaging showed es sentially equal lesion volumes 3 hours after MCA occlusion (195.4+/-61 mm(3) in the drug-treated group and 194.4+/-65 mm(3) in controls). At 4 hours, ischemic lesion size was 182.1+/-56.9 mm(3) in treated anima ls and 222.9+/-88.7 mm(3) in the controls (P=.24, NS). Perfusion imagi ng did not show a change of cerebral perfusion within ischemic brain r egions in the bFGF group during the infusion. No behavioral or physiol ogical side effects were observed. Conclusions bFGF is a safe and effe ctive treatment for focal cerebral ischemia in rats. We observed a mod est delayed difference of ischemic lesion size in vivo with diffusion MRI. The diffusion-weighted MRI findings suggest a potential delayed t herapeutic effect of bFGF, and the perfusion imaging findings imply th at the effect is not due to increased blood flow to the ischemic regio n.