Differential expression of fibroblast growth factor-2 and fibroblast growth factor receptor 1 in a scarring and nonscarring model of CNS injury in the rat

Injury to the adult brain results in abortive axon regeneration and the dep osition of a dense fibrous glial scar. Therapeutic strategies to promote po stinjury axon regeneration are likely to require antiscarring strategies. I n neonatal brain wounds, scar material is not laid down and axons grow acro ss the lesion site, either by de novo growth or regeneration. To achieve th e therapeutic goal of recapitulating the nonscarring neonatal response in t he injured adult, an understanding of how ontogenic differences in scarring reflect developmental diversities in the trophic response to injury is req uired. Fibrobast growth factor-2 (FGF-2) expression is developmentally regu lated and has been implicated as a regulator of the wounding response of th e adult rat central nervous system. We have investigated the expression of FGF-2 and fibroblast growth factor receptor 1 (FGFR1) after penetrating les ions to the cerebral cortex of 5 days post partum (dpp) (nonscarring) and 1 6 dpp and adult (scarring) rats. In situ hybridization, immunohistochemistr y and Western blotting showed robust and sustained increases in FGF-2 and F GFR1 mRNA and protein in reactive astrocytes around the lesion in scarring rats, a response that was attenuated substantially in the nonscarring neona te. These results demonstrate that changes in astrocyte FGF-2 and FGFR1 exp ression are coincident with the establishment of a mature pattern of glial scarring after injury in the maturing central nervous system, but it is pre mature to infer a causal relationship without further experiments.