Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / metabolism
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Antigens, Differentiation, Myelomonocytic / metabolism
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Cell Movement / drug effects
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Cell Movement / physiology
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Ciliary Neurotrophic Factor / pharmacology*
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Disease Models, Animal
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GAP-43 Protein / metabolism
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Gene Expression / drug effects*
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Gene Expression / physiology
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Growth Cones / drug effects
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Growth Cones / metabolism
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Growth Cones / pathology
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Histocompatibility Antigens Class II / metabolism
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Immunohistochemistry
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Janus Kinase 1 / metabolism
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Male
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Motor Neurons / drug effects
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Motor Neurons / metabolism
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Motor Neurons / pathology
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Nerve Regeneration / drug effects*
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Nerve Regeneration / physiology
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Prostheses and Implants
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Prosthesis Implantation / methods*
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Rats
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Rats, Sprague-Dawley
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S100 Proteins / metabolism
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STAT3 Transcription Factor / metabolism
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Schwann Cells / drug effects
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Schwann Cells / metabolism
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Sciatic Neuropathy / drug therapy*
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Sciatic Neuropathy / metabolism
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Sciatic Neuropathy / surgery*
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Silicones / therapeutic use
Substances
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD68 protein, rat
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Ciliary Neurotrophic Factor
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GAP-43 Protein
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Histocompatibility Antigens Class II
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S100 Proteins
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STAT3 Transcription Factor
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Silicones
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Stat3 protein, rat
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Janus Kinase 1