Regulation of astrocyte proliferation by FGF-2 and heparan sulfate in vivo.
The goal of this study was to examine the ability of basic fibroblast growth factor (FGF-2) to promote reactivity and/or proliferation of astrocytes in vivo following brain injury, and the possible mechanisms involved. A small bilateral lesion in the motor-sensory cortex was performed, and either FGF-2, FGF-2 plus heparan sulfate, heparan sulfate, or saline was applied unilaterally in a piece of Gelfoam within the wound cavity. Following lesions, there was an increase in FGF-2 and FGF receptor (FGFR) immunoreactivities in the area surrounding the lesion in all the treatment groups. Rats that received treatment with recombinant FGF-2 alone showed an increase in the density of astrocytes as compared to the control group. The same group of rats exhibited an increase in the density of cells displaying FGF-2 immunoreactivity and cells displaying FGFR-1 immunoreactivity and cells displaying FGFR-1 immunoreactivity, and also an induction of FGF-2 mRNA in the tissue surrounding the lesion. The group of rats that received FGF-2 combined with heparan sulfate showed a larger increase in the same cellular parameters. Our results suggest that the FGF-2/FGFR system is involved in the regulation of astrocytic reactivity and/or proliferation in the brain and its action is potentiated by heparan sulfate. The action of FGF-2 on CNS injury appears to be part of an autocrine cascade that involves induction of FGF-2 and its receptor, thereby enhancing the ability of astrocytes to respond to FGF-2.
Gómez-Pinilla
F
F
Department of Neurology, University of California, Irvine 92717.
Vu
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L
Cotman
C W
CW
D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism
D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor