Faster nerve regeneration after sciatic nerve injury in mice over-expressing basic fibroblast growth factor.
Basic fibroblast growth factor (FGF-2) is expressed in the peripheral nervous system and is up-regulated after nerve lesion. It has been demonstrated that administration of FGF-2 protects neurons from injury-induced cell death and promotes axonal regrowth. Using transgenic mice over-expressing FGF-2 (TgFGF-2), we addressed the importance of endogenously generated FGF-2 on sensory neuron loss and sciatic nerve regeneration. After sciatic nerve transection, wild-type and transgenic mice showed the same degree of cell death in L5 spinal ganglia. Also, the number of chromatolytic, eccentric, and pyknotic sensory neurons was not changed under elevated levels of FGF-2. Morphometric evaluation of intact nerves from TgFGF-2 mice revealed no difference in number and size of myelinated fibers compared to wild-type mice. One week after crush injury, the number of regenerated axons was doubled and the myelin thickness was significantly smaller in transgenic mice. After 2 and 4 weeks, morphometric analysis and functional tests revealed no differences in recovery of sensory and motor nerve fibers. To study the role of FGF-2 over-expression on Schwann cell proliferation during the early regeneration process, we used BrdU-labeling to mark dividing cells. In transgenic mice, the number of proliferating cells was significantly increased distal to the crush site compared to wild-types. We propose that endogenously synthesized FGF-2 influences early peripheral nerve regeneration by regulating Schwann cell proliferation, axonal regrowth, and remyelination.
Jungnickel
Julia
J
Department of Neuroanatomy OE 4140, Center of Anatomy, Hannover Medical School, D-30623 Hannover, Germany. jungnickel.julia@mh-hannover.de
Haase
Kristina
K
Konitzer
Jens
J
Timmer
Marco
M
Grothe
Claudia
C
D000818:Animals; D019771:Axotomy; D016923:Cell Death; D002455:Cell Division; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009186:Myelin Sheath / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D009475:Neurons, Afferent / Q000166:cytology*; D012583:Schwann Cells / Q000166:cytology; D012584:Sciatic Nerve / Q000293:injuries*
D016222:Fibroblast Growth Factor 2