UP-REGULATION OF FIBROBLAST GROWTH FACTOR-RECEPTOR MESSENGER-RNA EXPRESSION IN RAT-BRAIN FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA

Recently, we demonstrated that transient fore-brain ischemia in rats l eads to an early and strong induction of basic fibroblast growth facto r (bFGF) synthesis in astrocytes in the injured brain regions. In this study, in order to clarify the targets of such raised endogenous bFGF levels, the messenger RNA (mRNA) expression of its receptors (flg and bek) in the hippocampus following transient forebrain ischemia induce d by four-vessel occlusion for 20 min was investigated using an in sit u hybridization technique. Transient forebrain ischemia induced an inc rease in the number of flg mRNA-positive cells from an early stage (24 h after ischemia) in the hippocampal CA1 subfield where delayed neuro nal death occurred later (48-72 h after ischemia). This increase becam e more marked with the progression of neuronal death and was still evi dent in the same area 30 days later. The time course of the appearance and distribution pattern of flg mRNA-positive cells in the CA1 subfie ld were quite similar to those of bFGF mRNA-positive cells. On the oth er hand, in situ hybridization for bek mRNA showed only slight and tra nsient (observed 72 h and 5 days after ischemia) increases in the numb er of mRNA-positive cells in the CA1 subfield following ischemia. The use of in situ hybridization and glial fibrillary acidic protein immun ohistochemistry in combination demonstrated that the cells in the CA1 subfield that exhibited ischemia-induced flg or bek mRNA expression we re astrocytes. These data indicate that transient forebrain ischemia i nduces upregulation of fibroblast growth factor-receptor expression, a ccompanied by increased bFGF expression in astrocytes, and suggest tha t the increased astrocytic bFGF levels in injured brain regions act on the astrocytes via autocrine systems and are involved in the developm ent and maintenance of astrocytosis.