title: Fgf2 improves functional recovery-decreasing gliosis and increasing radial glia and neural progenitor cells after spinal cord injury.
abstract: OBJECTIVE
  A major impediment for recovery after mammalian spinal cord injury (SCI) is the glial scar formed by proliferating reactive astrocytes. Finding factors that may reduce glial scarring, increase neuronal survival, and promote neurite outgrowth are of major importance for improving the outcome after SCI. Exogenous fibroblast growth factor (Fgf) has been shown to decrease injury volume and improve functional outcome; however, the mechanisms by which this is mediated are still largely unknown.
  
  
  METHODS
  In this study, Fgf2 was administered for 2 weeks in mice subcutaneously, starting 30 min after spinal cord hemisection.
  
  
  RESULTS
  Fgf2 treatment decreased the expression of TNF-a at the lesion site, decreased monocyte/macrophage infiltration, and decreased gliosis. Fgf2 induced astrocytes to adopt a polarized morphology and increased expression of radial markers such as Pax6 and nestin. In addition, the levels of chondroitin sulfate proteoglycans (CSPGs), expressed by glia, were markedly decreased. Furthermore, Fgf2 treatment promotes the formation of parallel glial processes, "bridges," at the lesion site that enable regenerating axons through the injury site. Additionally, Fgf2 treatment increased Sox2-expressing cells in the gray matter and neurogenesis around and at the lesion site. Importantly, these effects were correlated with enhanced functional recovery of the left paretic hind limb.
  
  
  CONCLUSIONS
  Thus, early pharmacological intervention with Fgf2 following SCI is neuroprotective and creates a proregenerative environment by the modulation of the glia response.
authors.affiliation: Australian Regenerative Medicine Institute East Melbourne, VIC, Australia ; Centre for Eye Research Australia & Royal Victorian Eye and Ear Hospital East Melbourne, VIC, Australia.
authors.forename: Yona
authors.initials: Y
authors.lastname: Goldshmit
authors.affiliation: Department of Ophthalmology, The University of Melbourne East Melbourne, VIC, Australia.
authors.forename: Frisca
authors.initials: F
authors.lastname: Frisca
authors.affiliation: Australian Regenerative Medicine Institute East Melbourne, VIC, Australia.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Pinto
authors.affiliation: Centre for Eye Research Australia & Royal Victorian Eye and Ear Hospital East Melbourne, VIC, Australia ; Department of Ophthalmology, The University of Melbourne East Melbourne, VIC, Australia.
authors.forename: Alice
authors.initials: A
authors.lastname: Pébay
authors.affiliation: Australian Regenerative Medicine Institute East Melbourne, VIC, Australia.
authors.forename: Jean-Kitty K Y
authors.initials: JK
authors.lastname: Tang
authors.affiliation: Australian Regenerative Medicine Institute East Melbourne, VIC, Australia.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Siegel
authors.affiliation: Australian Regenerative Medicine Institute East Melbourne, VIC, Australia.
authors.forename: Jan
authors.initials: J
authors.lastname: Kaslin
authors.affiliation: Australian Regenerative Medicine Institute East Melbourne, VIC, Australia.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Currie
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005911:Gliosis / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects*; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D058630:Spinal Cord Regeneration / Q000187:drug effects*
chemical_list: D016222:Fibroblast Growth Factor 2
keywords: Astroglia; GFAP; Pax6; Sox2; nestin; progenitors; regeneration; spinal cord injury