Related Experiment Videos
Effect of basic fibroblast growth factor on experimental focal ischemia studied by diffusion-weighted and perfusion
T Tatlisumak1, K Takano, R A Carano
1Department of Neurology, Helsinki University Central Hospital, Finland.
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 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.
Insights
Basic fibroblast growth factor (bFGF) reduced infarct size in rats with focal cerebral ischemia. This neuroprotective agent demonstrated a delayed therapeutic effect without increasing blood flow, suggesting a novel treatment strategy.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Basic fibroblast growth factor (bFGF) exhibits known neuroprotective properties.
- Focal cerebral ischemia can lead to significant brain damage.
Purpose of the Study:
- To evaluate the therapeutic effects of bFGF on infarct size.
- To assess bFGF's impact when administered 30 minutes post-ischemia.
- To investigate bFGF's mechanism using MRI.
Main Methods:
- 20 rats underwent middle cerebral artery (MCA) occlusion.
- Rats were randomized to receive bFGF or vehicle infusion.
- Diffusion-weighted and perfusion MRI monitored lesion development.
- Infarct volume was quantified postmortem using TTC staining.
Main Results:
- bFGF treatment significantly reduced infarct volume postmortem (P = .038).
- Diffusion MRI showed no immediate difference in lesion size between groups.
- A modest, delayed reduction in ischemic lesion size was observed with bFGF.
- Perfusion imaging revealed no increase in blood flow to ischemic regions.
Conclusions:
- bFGF is a safe and effective treatment for focal cerebral ischemia in rats.
- The study suggests a potential delayed therapeutic effect of bFGF.
- The therapeutic effect appears independent of increased cerebral perfusion.