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Intravenous basic fibroblast growth factor does not ameliorate brain injury resulting from transient focal ischemia
I Harukuni1, R J Traystman, A Bhardwaj
1Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Insights
Intravenous basic fibroblast growth factor (bFGF) did not protect against brain injury in a cat model of transient focal ischemia. The study found no significant difference in injury volume or neurologic scores between bFGF-treated and control groups.
Area of Science:
- Neuroscience
- Ischemic Stroke Research
- Pharmacology
Background:
- Transient focal ischemia can lead to significant brain injury.
- Basic fibroblast growth factor (bFGF) has shown potential in preclinical models for neuroprotection.
- Investigating novel therapeutic targets for stroke is crucial.
Purpose of the Study:
- To evaluate the neuroprotective effects of intravenous basic fibroblast growth factor (bFGF) in a feline model of transient focal cerebral ischemia.
- To determine if bFGF administration can reduce brain infarction volume and improve neurological outcomes post-ischemia.
- To test the hypothesis that bFGF inhibits brain injury development during focal ischemia.
Main Methods:
- Thirty-nine Halothane-anesthetized cats underwent 60-minute middle cerebral artery occlusion.
- Experimental groups received intravenous bFGF (2 or 5 microg/kg/hour) starting 45 minutes after ischemia onset until 24 hours of reperfusion.
- Control groups received diluent; neurologic function and infarction volume were assessed post-reperfusion.
Main Results:
- No significant difference in hemisphere injury volume or neurologic evaluation scores was observed between control and bFGF-treated groups (2 or 5 microg/kg/hour).
- Mortality rates were higher in cats treated with bFGF (3/13 at 2 microg/kg/hour, 6/16 at 5 microg/kg/hour) compared to potential implicit control survival.
- The data did not support a neuroprotective effect of intravenous bFGF in this model.
Conclusions:
- Intravenous administration of basic fibroblast growth factor (bFGF) did not demonstrate neuroprotective efficacy in a cat model of transient focal cerebral ischemia.
- The study failed to support the hypothesis that bFGF inhibits brain injury development under the tested conditions.
- Further research may be needed to explore alternative delivery methods or dosages if bFGF is to be considered for stroke treatment.
Abstract:
This study sought to test the hypothesis that intravenous basic fibroblast growth factor (bFGF) inhibits the development of brain injury during transient focal ischemia. Halothane-anesthetized cats (n=39) underwent left middle cerebral artery occlusion for 60 minutes. After the onset of reperfusion, wounds were closed and the cats were allowed to emerge from anesthesia. Experimental cats were treated with intravenous bFGF at a dose of either 2 or 5 microg/kg per hour, beginning 45 minutes after initiation of ischemia and continuing until 24 hours of reperfusion, when neurologic function and infarction volume were evaluated. The cats in the control group received diluent. Three of thirteen cats treated with bFGF 2 microg/kg/hour and six of sixteen cats treated with bFGF 5 microg/kg/hour died during the 24 hour reperfusion period. There was no difference in injury volume or neurologic evaluation score in the control group (n=10; hemisphere injury, 1301+/-306 mm3, mean+/-SE; score 53+/-3), and cats treated with either 2 microg/kg/hour (n=10; hemisphere injury, 1170+/-292 mm3; score 50+/-3) or 5 microg/kg/hour bFGF (n=10; hemisphere injury, 1343+/-374 mm3; score 50+/-2). The data collected do not support the hypothesis that intravenous bFGF is neuroprotective in a cat model of transient focal ischemia.