Fibroblast growth factor-2 induces astroglial and microglial reactivity in vivo

A role for fibroblast growth factor-2 (FGF-2) has been proposed in mediating the glial response to injury in the central nervous system (CNS). We have tested this possibility in vivo, by injecting FGF-2 into the cerebrospinal fluid (CSF) of the brain ventricles of young rats and analysing glial cells in the anterior medullary velum (AMV), which partly roofs the IVth ventricle. FGF-2 was administered at two different doses, low FGF-2 (500 ng mL(-1) CSF) and high FGF-2 (10 microg mL(-1) CSF), and saline vehicle was injected in controls. Injections were performed twice daily for three days, commencing at postnatal day (P) 6, and AMV were analysed at P9, using immunohistochemistry and Western blotting. Glial cells were unaffected by treatment with saline or low FGF-2, whereas high FGF-2 induced reactive changes in glial cell types: (1) there was increased GFAP expression in astrocytes, demonstrated by Western blot and immunohistochemistry, and astrocytes appeared hypertrophic, with increased process thickness and number; (2) the number of ED1 labelled microglia/macrophages was doubled, from 47 +/- 6 to 114 +/- 17 cells per field (0.75 mm2; values are mean +/- SEM), and microglia appeared activated, with a multipolar and granular appearance; (3) NG2 positive glial cells appeared more fibrous and there was increased density of processes, although there was no significant increase in their number; (4) oligodendrocyte somata were enlarged and there was a loss of myelin sheaths. The results show that at high CSF titres of FGF-2 induce glial reactivity in vivo and support a role for FGF-2 in the pathology of CNS injury and EAE.