Physiological function and putative therapeutic impact of the FGF-2 system in peripheral nerve regeneration--lessons from in vivo studies in mice and rats

Brain Res Rev. 2006 Aug;51(2):293-9. doi: 10.1016/j.brainresrev.2005.12.001. Epub 2006 Jan 23.


Diffusible and substratum-bound molecules regulate development and regeneration of the peripheral nervous system. The understanding of physiological function of these factors could have an impact on the development of new therapeutic strategies to stimulate nerve regeneration across long gaps. Within the group of trophic factors, basic fibroblast growth factor (FGF-2) and its high-affinity receptors are expressed in the intact peripheral nervous system and regulated following nerve injury. After exogenous application, FGF-2 promotes neuronal survival and neurite outgrowth in vitro and in vivo. In this review, animal studies on the physiological role of the endogenous FGF-2 system and the regenerative capacity after exogenous FGF-2 administration are summarized. The concept of FGF-2 function is discussed in context with other growth factors that are also physiologically relevant in the peripheral nervous system. Studies of sciatic nerve axotomy in FGF-2- and FGF receptor (R) 3-deleted mice, respectively, strongly suggested that FGF-2 binding to FGFR3 is involved in injury-induced neuronal apoptosis. At the lesion site, inhibition of myelination and stimulation of Schwann cell proliferation by FGF-2 via FGFR1/2 is suggested from rat and mouse studies, whereas neurite formation is very likely enhanced via FGFR3 activation. Additionally to these demonstrated physiological functions of endogenous FGF-2, administration of FGF-2 isoforms in the rat model of nerve regeneration across long gaps revealed a role of the high molecular weight isoforms of FGF-2 on sensory recovery. Within the group of physiologically relevant trophic factors, the FGF-2 system seems to be crucially involved in the scenario of peripheral nerve development and regeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Disease Models, Animal
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Fibroblast Growth Factor 2 / therapeutic use
  • Humans
  • Mice
  • Mice, Mutant Strains
  • Myelin Sheath / metabolism
  • Myelin Sheath / ultrastructure
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology*
  • Peripheral Nerves / cytology
  • Peripheral Nerves / growth & development
  • Peripheral Nerves / metabolism*
  • Rats
  • Receptors, Fibroblast Growth Factor / drug effects
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Schwann Cells / cytology
  • Schwann Cells / metabolism


  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 2