title: C3 peptide promotes axonal regeneration and functional motor recovery after peripheral nerve injury.
abstract: Peripheral nerve injuries are frequently seen in trauma patients and due to delayed nerve repair, lifelong disabilities often follow this type of injury. Innovative therapies are needed to facilitate and expedite peripheral nerve regeneration. The purpose of this study was to determine the effects of a 1-time topical application of a 26-amino-acid fragment (C3(156-181)), derived from the Clostridium botulinum C3-exoenzyme, on peripheral nerve regeneration in 2 models of nerve injury and repair in adult rats. After sciatic nerve crush, different dosages of C3(156-181) dissolved in buffer or reference solutions (nerve growth factor or C3(bot)-wild-type protein) or vehicle-only were injected through an epineurial opening into the lesion sites. After 10-mm nerve autotransplantation, either 8.0 nmol/kg C3(156-181) or vehicle were injected into the proximal and distal suture sites. For a period of 3 to 10 postoperative weeks, C3(156-181)-treated animals showed a faster motor recovery than control animals. After crush injury, axonal outgrowth and elongation were activated and consequently resulted in faster motor recovery. The nerve autotransplantation model further elucidated that C3(156-181) treatment accounts for better axonal elongation into motor targets and reduced axonal sprouting, which are followed by enhanced axonal maturation and better axonal functionality. The effects of C3(156-181) are likely caused by a nonenzymatic down-regulation of active RhoA. Our results indicate the potential of C3(156-181) as a therapeutic agent for the topical treatment of peripheral nerve repair sites.
authors.affiliation: Hannover Medical School, Institute of Toxicology, Hannover, Germany.
authors.forename: Stefanie C
authors.initials: SC
authors.lastname: Huelsenbeck
authors.forename: Astrid
authors.initials: A
authors.lastname: Rohrbeck
authors.forename: Annelie
authors.initials: A
authors.lastname: Handreck
authors.forename: Gesa
authors.initials: G
authors.lastname: Hellmich
authors.forename: Eghlima
authors.initials: E
authors.lastname: Kiaei
authors.forename: Irene
authors.initials: I
authors.lastname: Roettinger
authors.forename: Claudia
authors.initials: C
authors.lastname: Grothe
authors.forename: Ingo
authors.initials: I
authors.lastname: Just
authors.forename: Kirsten
authors.initials: K
authors.lastname: Haastert-Talini
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000187:drug effects*; D003176:Complement C3 / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007839:Functional Laterality; D047468:Immunoprecipitation; D009043:Motor Activity / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D018709:Statistics, Nonparametric; D013997:Time Factors; D016378:Tissue Transplantation / Q000379:methods; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D003176:Complement C3; D010455:Peptides; D020742:rhoA GTP-Binding Protein