Influence of EGF/bFGF treatment on proliferation, early neurogenesis and infarct volume after transient focal ischemia.

The persistence of neurogenesis in the adult mammalian forebrain suggests that endogenous precursors may be a potential source for neuronal replacement after injury or neurodegeneration. On the other hand basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) can facilitate neural precursor proliferation in the adult rodent subventricular zone (SVZ) and dentate gyrus. As the application of EGF and bFGF was found to boost neurogenesis after global ischemia, in this study we investigated whether a combined intracerebroventricular (i.c.v.) EGF/bFGF treatment over a period of 2 weeks affects the proliferation of newly generated cells in the endothelin-1 model of transient focal ischemia in adult male Sprague-Dawley rats as well. As assessed by toluidine blue staining, EGF/bFGF substantially increased the infarct volume in ischemic animals. Chronic 5'-bromodeoxyuridine (BrdU) i.c.v. application revealed an EGF/bFGF-induced increase in cell proliferation in the lateral ventricle 14 days after surgery. Proliferation in the striatum increased after ischemia, whereas in the dentate gyrus and in the dorsal 3rd ventricle the number of cells decreased. Analysis of the neuronal fate of these cells by co-staining with a doublecortin (DCX) antibody showed that the growth factors concomitantly nearly doubled early neurogenesis in the ipsilateral striatum in ischemic animals but diminished it in the dentate gyrus. Because of the increased infarct volume and unclear long-term outcome further modifications of a chronic treatment schedule are needed before final conclusions concerning the perspectives of such an approach can be made.