Different Patterns of Induction of Fibroblast Growth Factor‐2 and Brain‐Derived Neurotrophic Factor Messenger RNAs During Kindling Epileptogenesis, and Development of a Herpes Simplex Vector for Fibroblast Growth Factor‐2 Gene Transfer in Vivo

Summary: Purpose : To investigate the gene expression patterns of brain‐derived neurotrophic factor (BDNF) and fibroblast growth factor‐2 (FGF‐2) in the kindling model, and to construct a replication‐defective herpes simplex virus vector to induce expression of FGF‐2 in vivo. Methods : RNase protection assay and herpes simplex virus vector (TH FGF‐2) deleted in the immediate‐early genes ICP4, ICP22, and ICP27, with FGF‐2 inserted in tk under the control of the human cytomegalovirus immediate‐early promoter. Results : A single kindling stimulation did not modify BDNF gene expression, whereas it increased FGF‐2 messenger RNA (mRNA) levels in the hippocampus, the cortex, and the hypothalamus. BDNF and FGF‐2 gene expression were not altered in kindled animals left unstimulated for 1 week. In contrast, kindled seizures produced a great increase in hippocampal and cortical BDNF mRNA levels, but FGF‐2 mRNA was increased only in the ipsilateral cortex. Infection of Vero cells with TH FGF‐2 resulted in a long‐lasting increase in FGF‐2 levels. Protein extracts of infected cells induced neuronal differentiation of PC12 cells, indicating that the newly synthesized FGF‐2 was biologically active. Robust transient transgene expression was observed in the rat hippocampus after inoculation with TH FGF‐2 in the absence of significant toxicity. Conclusions : BDNF and FGF‐2 are recruited at different stages of kindling and, accordingly, may play different roles in the adaptive changes taking place during epileptogenesis. TH FGF‐2 is suitable for studies of FGF‐2 involvement in kindling epileptogenesis.