INCREASED EXPRESSION OF BASIC FIBROBLAST GROWTH-FACTOR (BFGF) FOLLOWING FOCAL CEREBRAL INFARCTION IN THE RAT

Basic fibroblast growth factor (bFGF) is a polypeptide with potent tro phic effects on brain neurons, glia, and endothelial cells. In the cur rent study, we used Northern blotting, in situ hybridization, and immu nohistochemical techniques to examine bFGF expression in brain followi ng focal infarction due to permanent occlusion of the proximal middle cerebral artery in mature Sprague-Dawley rats. We found a four-fold in crease in bFGF mRNA in tissue surrounding focal infarcts at 1 day afte r ischemia. In situ hybridization showed that this increase was found throughout several structures in the ipsilateral hemisphere, including frontoparietal, temporal, and cingulate cortex, as well as in caudopu tamen, globus pallidus, septal nuclei, nucleus accumbens, and olfactor y tubercle. Increased bFGF mRNA expression was associated with cells h aving the distinct morphological appearance of astroglia in these stru ctures. Immunohistochemistry showed an increase in the size and number of bFGF-immunoreactive (IR) nuclei in these same structures, as well as a shift from nuclear to nuclear plus cytoplasmic localization of im munoreactivity, beginning at 1 day, and peaking at 3 days after ischem ia. Double immunostaining identified bFGF-IR cells as astroglia in the se structures. (An exception was the piriform cortex, in which both in creased bFGF mRNA levels and increased bFGF-IR was found in neurons at 1 day after ischemia.) Overall, the peak of increased bFGF expression preceded the peak in expression of the astroglial marker GFAP within the ipsilateral hemisphere. Increased bFGF expression may play an impo rtant role in the glial, neuronal, and vascular changes occurring afte r focal infarction.