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 deposition of a dense fibrous glial scar. Therapeutic strategies to promote postinjury axon regeneration are likely to require antiscarring strategies. In neonatal brain wounds, scar material is not laid down and axons grow across the lesion site, either by de novo growth or regeneration. To achieve the therapeutic goal of recapitulating the nonscarring neonatal response in the injured adult, an understanding of how ontogenic differences in scarring reflect developmental diversities in the trophic response to injury is required. Fibrobast growth factor-2 (FGF-2) expression is developmentally regulated and has been implicated as a regulator of the wounding response of the adult rat central nervous system. We have investigated the expression of FGF-2 and fibroblast growth factor receptor 1 (FGFR1) after penetrating lesions to the cerebral cortex of 5 days post partum (dpp) (nonscarring) and 16 dpp and adult (scarring) rats. In situ hybridization, immunohistochemistry and Western blotting showed robust and sustained increases in FGF-2 and FGFR1 mRNA and protein in reactive astrocytes around the lesion in scarring rats, a response that was attenuated substantially in the nonscarring neonate. These results demonstrate that changes in astrocyte FGF-2 and FGFR1 expression are coincident with the establishment of a mature pattern of glial scarring after injury in the maturing central nervous system, but it is premature to infer a causal relationship without further experiments.
Smith
C
C
Department of Medicine, University of Birmingham, Birmingham B15 2TT, UK.
Berry
M
M
Clarke
W E
WE
Logan
A
A
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000737:chemistry / Q000293:injuries / Q000503:physiopathology*; D002921:Cicatrix / Q000503:physiopathology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000235:genetics*
D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1