The role of basic fibroblast growth factor in peripheral nerve regeneration

Abstract

In the peripheral nervous system regeneration and gradual functional restoration occur following peripheral nerve injury. Growth of regenerating axons depends on the presence of diffusible neurotrophic factors, in addition to the substratum. Neurotrophic factors that are involved in peripheral nerve regeneration include nerve growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor, glial cell line-derived neurotrophic factor, and interleukin-6. Recent functional and expression studies of basic fibroblast growth factor and its receptors have emphasized a physiological role of these molecules in the peripheral nervous system. Basic fibroblast growth factor and its receptors are constitutively expressed in dorsal root ganglia and the peripheral nerve. These molecules display an upregulation in dorsal root ganglia and in the proximal and distal nerve stumps following peripheral nerve injury. In the ganglia these molecules show a mainly neuronal expression, whereas at the lesion site of the nerve, Schwann cells and invading macrophages represent the main cellular sources of basic fibroblast growth factor and the receptors 1-3. Exogenously applied basic fibroblast growth factor mediates rescue effects on injured sensory neurons and supports neurite outgrowth of transectioned nerves. Regarding the expression patterm and the effects after exogenous administration of basic fibroblast growth factor, this molecule seems to play a physiological role during nerve regeneration. Thus, basic fibroblast growth factor could be a promising candidate to contribute to the development of new therapeutic strategies for the treatment of peripheral nerve injuries.

Fibroblast Growth Factor (FGF)-2 and FGF Receptor 3 Are Required for the Development of the Substantia Nigra, and FGF-2 Plays a Crucial Role for the Rescue of Dopaminergic Neurons after 6-Hydroxydopamine Lesion

“…After peripheral nerve injury, FGFR3 was upregulated in contrast to the other FGF-2 receptors (Ji et al, 1995;Grothe and Nikkhah, 2001). Furthermore, this receptor is crucially involved in the regulation of survival of sensory neurons after lesion but not during peripheral nerve development (Jungnickel et al, 2004a(Jungnickel et al, , 2005.…”

Differentially promoted peripheral nerve regeneration by grafted Schwann cells over-expressing different FGF-2 isoforms

“…Furthermore, it has been shown previously that entrapment of the low molecular weight (18-kDa) isoform of fibroblast growth factor-2 (FGF-2) in synthetic nerve guidance channels is able to enhance growth of myelinated and unmyelinated axons across long gaps significantly (Aebischer et al, 1989). With regard to the low and high molecular weight FGF-2 isoforms, it has been shown that the isoforms are differentially regulated following peripheral nerve injury, indicating differential physiological functions during peripheral nerve regeneration (for review, see: Grothe and Nikkhah, 2001). Non-resorbable silicone tubes were introduced as an experimental model for tubulization in peripheral nerve repair.…”

Effects of Basic Fibroblast Growth Factor on Experimental Diabetic Neuropathy in Rats

“…The half-life time of bFGF is relatively short (24), and cross-linked gelatin hydrogel (CGH) has been used to maintain the bioactivity of locally administered bFGF for an extended period (25,26). Furthermore, it has been reported that bFGF has effects on the central nervous system (27,28) and peripheral nervous system (29,30). However, the effects of bFGF on diabetic neuropathy have not been investigated.…”