Effect of basic fibroblast growth factor on experimental focal ischemia studied by diffusion-weighted and perfusion imaging.
OBJECTIVE
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 micrograms/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.
Tatlisumak
T
T
Department of Neurology, Helsinki University Central Hospital, Finland.
Takano
K
K
Carano
R A
RA
Fisher
M
M
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002536:Cerebral Arteries; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003250:Constriction; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D015424:Reperfusion
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2