Recombinant ciliary neurotrophic factor promotes nerve regeneration and induces gene expression in silicon tube-bridged transected sciatic nerves in adult rats.
Sciatic nerves in adult male rats were transected and reunited via a silicone chamber. This was followed by a focal injection of recombinant ciliary neurotrophic factor (CNTF). To evaluate the effect of this therapeutic approach and to explore its possible mechanisms, nerve regeneration was traced by horseradish peroxidase retrograde labeling. Functional recovery was evaluated by functional assessment of the hind feet and the expression of a number of proteins was detected using immunohistochemistry. The results showed that a single administration of CNTF could promote regeneration of motor axons, with improved functional recovery in adult rats. Growth associated protein (GAP)-43, S100, CD68 and major histocompatibility complex class II immunoreactivity in the regenerative and distal nerves suggested that CNTF could promote axon regeneration, Schwann cell migration, monocyte infiltration and activation. CNTF might also indirectly promote axonal regeneration by further activating the JAK-STAT3 pathway and subsequently upregulating phosphotyrosine, GAP-43 and S100 expression to enhance proliferation, growth and migration of Schwann cells. CNTF has suggested important targets for pharmacological intervention in peripheral nerve disease and injury.
Xu
Jia-jun
JJ
Department of Anatomy, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. jjxu@smmu.edu.cn
Chen
Er-yu
EY
Lu
Chang-lin
CL
He
Cheng
C
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007150:Immunohistochemistry; D053613:Janus Kinase 1 / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D019736:Prostheses and Implants; D019919:Prosthesis Implantation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D012828:Silicones / Q000627:therapeutic use; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D020934:Ciliary Neurotrophic Factor; D019922:GAP-43 Protein; D000949:Histocompatibility Antigens Class II; D053613:Janus Kinase 1; D009418:S100 Proteins; D050796:STAT3 Transcription Factor; D012828:Silicones; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C494088:Stat3 protein, rat