INDUCTION OF BASIC FIBROBLAST GROWTH-FACTOR (BFGF) EXPRESSION FOLLOWING FOCAL CEREBRAL-ISCHEMIA

Basic fibroblast growth factor (bFGF) is a biologically active polypep tide with mitogenic, angiogenic, and neurotrophic properties. In the p resent study, we examined the temporal and spatial expression profiles of bFGF mRNA and protein concentration in a focal cerebral ischemia m odel induced by transient occlusion of the right middle cerebral arter y (MCA) and both common carotid arteries (CCAs). Results of Northern b lot analysis shows a transient 2.5-fold increase in the 6.0 kb transcr ipt of bFGF mRNA within the ischemic cortex of rats subjected to 60 mi n ischemic insult followed by 12 h of reperfusion. Although enhanced e xpression of bFGF mRNA was also noted in the ipsilateral hippocampus, the temporal induction profile appeared to be different from that of t he ischemic cortex. A significant increase in bFGF mRNA was observed a s early as 60 min following ischemia and remained elevated for up to 2 weeks after the onset of reperfusion. In situ hybridization studies r evealed constitutive expression of bFGF mRNA in discrete brain regions of sham-operated animals. Following 60 min ischemia and 12 h reperfus ion, increased expression of bFGF mRNA was observed in the ischemic co rtex (both peri-infarct and infarct area). Increased expression of bFG F mRNA within the infarcted area is largely confined rostrally to the outer cortical layers of the infarct, an area with increased density o f blood vessels. bFGF-like immunoreactivity was also detected in areas expressing bFGF mRNA. Furthermore, a striking increase in bFGF-like i mmunoreactivity was observed in the ipsilateral hippocampus. Double-st aining with anti-GFAP antibody indicated that the majority of the bFGF -like immunoreactivity was localized in the astrocytes, however, not a ll astrocytes showed bFGF-like immunoreactivity. Some GFAP negative ce ll also showed bFGF-like immunoreactivity. In summary, increased expre ssion of both bFGF mRNA and immunoreactivity following ischemia were l ocated in the same brain regions. An increase in bFGF-like immunoreact ivity after ischemic insult is likely due to an increase in the expres sion of its 6.0 kb bFGF mRNA transcripts. Although increased bFGF mRNA was observed in both ischemic cortex and ipsilateral hippocampus afte r ischemic insult, the temporal expression profiles differed. Results from the present study raise the possibility that increased expression of bFGF in the peri-infarcted area may limit the spread of ischemic i njury. (C) 1997 Elsevier Science B.V.