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Intravenous basic fibroblast growth factor decreases brain injury resulting from focal ischemia in cats
A Bethel1, J R Kirsch, R C Koehler
1Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md 21287, USA.
Insights
Basic fibroblast growth factor (bFGF) reduced acute brain injury in cats with focal ischemia. This neuroprotective effect occurred without altering blood flow, suggesting bFGF limits injury progression in ischemic areas.
Area of Science:
- Neuroscience
- Ischemic Stroke Research
- Biomedical Research
Background:
- Focal cerebral ischemia can lead to significant acute brain injury.
- Basic fibroblast growth factor (bFGF) is a potent growth factor with potential therapeutic applications.
- Investigating the role of bFGF in mitigating ischemic brain damage is crucial.
Purpose of the Study:
- To test if intravenous bFGF administration during focal cerebral ischemia affects acute brain injury in a feline model.
- To determine the dose-dependent effects of bFGF on cerebral injury.
- To assess the impact of bFGF on cerebral blood flow during ischemia.
Main Methods:
- Permanent focal ischemia was induced in cats via middle cerebral artery (MCA) occlusion for 4 hours.
- Experimental groups received intravenous bFGF at varying doses (5, 50, or 250 microg/kg per hour) starting 60 minutes after ischemia onset.
- Control groups received a diluent, and cerebral blood flow was measured using the microsphere method.
Main Results:
- bFGF administration significantly reduced the injury volume in the ipsilateral cerebral cortex.
- No significant differences in blood flow to the caudate nucleus or temporal cortex were observed between groups.
- Injury volume in the caudate nucleus and somatosensory evoked potential amplitude remained unaffected by bFGF treatment.
Conclusions:
- Systemic administration of bFGF ameliorates acute cerebral cortical injury following focal ischemia in cats.
- bFGF exerts its neuroprotective effects without increasing cerebral blood flow during ischemia.
- The findings suggest bFGF may limit the progression of injury in ischemic border zones, offering a potential therapeutic strategy.
Background And Purpose:
We tested the hypothesis that intravenous administration of basic fibroblast growth factor (bFGF) during 4 hours of permanent focal ischemia would affect acute brain injury.
Methods:
Halothane-anesthetized cats underwent left middle cerebral artery (MCA) occlusion for 4 hours. Control cats received diluent (n = 14). Experimental cats were treated with bFGF at a rate of 5 (n = 13), 50 (n = 13), or 250 microg/kg per hour (n = 9) intravenously beginning 60 minutes after initiation of ischemia and continuing until the end of the protocol.
Results:
As measured by the microsphere method, blood flow to ipsilateral caudate nucleus and ipsilateral inferior temporal cortex was decreased similarly during ischemia, before drug administration, in all groups. Likewise, there was no difference in blood flow to ipsilateral caudate nucleus or inferior temporal cortex as a result of bFGF administration during MCA occlusion. Triphenyltetrazolium-determined injury volume of the ipsilateral cerebral cortex (control, 40+/-7%; bFGF 5 microg/kg per hour, 22+/-5%; bFGF 50 microg/kg per hour, 26+/-7%; bFGF 255 microg/kg per hour, 23+/-6% of ipsilateral cerebral cortex; mean+/-SEM) was less in cats treated with bFGF. There was no difference among groups in injury volume to caudate nucleus (control, 29+/-8%; bFGF 5 microg/kg per hour, 29+/-8%; bFGF 50 microg/kg per hour, 21+/-7%; bFGF 250 microg/kg per hour, 32+/-7% of ipsilateral caudate nucleus). Somatosensory evoked potential amplitude decreased similarly (to <20% of baseline amplitude in all groups) during MCA occlusion and was not altered by bFGF administration. CONCLUSIONS; These data indicate that systemic administration of bFGF ameliorates acute injury in the cerebral cortex without increasing blood flow during focal ischemia in cats. Because bFGF afforded protection when administered after the onset of ischemia, bFGF may provide its beneficial effect by limiting progression of injury in ischemic border regions.