Application of FGF to the restoration of ischemic brain damage

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The present study was designed to investigate the application of basic fibroblast growth factor (bFGF) to restoration of ischemic cerebral damage. The investigators proposed research projects such as expression of bFGF mRNA and immediate early genes (IEGs) after the cerebral ischemia, and the neuroprotective effects of bFGF to ameliorate infarction volume. The following results were obtained. (1)EXPRESSION OF bFGF GENE AFTER TRANSIENT FOCAL ISCHEMIA : bFGF mRNA was markedly expressed in the peri-infarct cortex and caudoputamen during 6-48 hr after the reperfusion, and disappeared by 5 days. The expression of bFGF was also observed in the remote areas such as bilateral hippocampus and cingulate cortex. Signals of bFGF mRNA focused on neurons and glial cells. Previous reports showed that bFGF receptor mRNA was upregulated in the peri-infarct areas. Intrinsic bFGF released from the damaged tissue could influence the healing response through the auto-paracrine manner. Because IEGs preceded the bFGF mRNA expression, IEGs might regulate the bFGF transcription (Iwata A et al.J Neurotrauma 1997). (2)THE EFFECTS OF INTRAVENOUS bFGF ADMINISTRATION ON THE INFARCT SIZE : Permanent focal ischemia was made in rats. Thirty min after the initiation of ischemia, human recombinant bFGF was given intravenously for 3 days using osmotic minipumps. Infarct volumes in the rats treated with bFGF were significantly smaller than in the saline treated controls. Dose-dependency was present within 0.4 to 2 mug/kg/hr. Infarct volume increased at the dose of 10 mug/kg/h, probably as a result of hypotension. The reduction of infarction size was obvious in cortex rather than in caudate-putamen. Our study confirmed that long-term and low-dose intravenous administration of bFGF was potentially neuroprotective against focal ischemia without systemic side effects. (3)ONGOING PROJECT : The investigation of behavioral and physiological effects are in progress.