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(Stroke. 1996;27:2292-2298.)
© 1996 American Heart Association, Inc.

Articles

Effect of Basic Fibroblast Growth Factor on Experimental Focal Ischemia Studied by Diffusion-Weighted and Perfusion Imaging

Turgut Tatlisumak, MD; Kentaro Takano, MD, PhD; Richard A.D. Carano, MS Marc Fisher, MD

the Department of Neurology, Helsinki University Central Hospital, Finland (T.T.); the Department of Neurology, The Medical Center of Central Massachusetts (T.T., K.T., M.F.), the Department of Biomedical Engineering, Worcester Polytechnic Institute (R.A.D.C.), and the Departments of Radiology and Neurology, University of Massachusetts Medical School (M.F.), Worcester, Mass.

Background and Purpose Basic fibroblast growth factor (bFGF) has documented neuroprotective properties. This study was performed to evaluate the effects of bFGF on infarct size when administered 30 minutes after 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 vehicle (n=10). The animals underwent middle cerebral artery (MCA) occlusion using the suture model. Diffusion-weighted MRI was initiated 30 minutes after induction of ischemia and repeated frequently for 3.5 hours. Drug (45 µg/kg per hour) or vehicle (saline) infusion began 30 minutes 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 TTC-derived, corrected infarct volume postmortem in the bFGF-treated group was significantly smaller than that in controls (126.6±51.9 versus 180.2±54.9 mm³, mean±SD, P=.038). Diffusion imaging showed essentially equal lesion volumes 3 hours after MCA occlusion (195.4±61 mm³ in the drug-treated group and 194.4±65 mm³ in controls). At 4 hours, ischemic lesion size was 182.1±56.9 mm³ in treated animals and 222.9±88.7 mm³ in the controls (P=.24, NS). Perfusion imaging did not show a change of cerebral perfusion within ischemic brain regions in the bFGF group during the infusion. No behavioral or physiological side effects were observed.

Conclusions bFGF is a safe and effective treatment for focal cerebral ischemia in rats. We observed a modest delayed difference of ischemic lesion size in vivo with diffusion MRI. The diffusion-weighted MRI findings suggest a potential delayed therapeutic effect of bFGF, and the perfusion imaging findings imply that the effect is not due to increased blood flow to the ischemic region.

Editorial Comment

Chang Y. Hsu, MD, PhD, Guest Editor

Cerebrovascular Disease SectionDepartment of NeurologyWashington University School of MedicineSt Louis, Mo

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