title: Ibuprofen improves functional outcome after axotomy and immediate repair in the peripheral nervous system.
abstract: BACKGROUND
  Activation of the Small GTP-binding protein Rho following the nerve injury contributes to the lack of regeneration in the peripheral nervous system. By elucidating the mechanisms leading to Rho activation, a nonsteroidal anti-inflammatory drug ibuprofen has been identified as a potent inhibitor of Rho activity. In this study we tested the hypothesis, that inhibiting Rho activity by ibuprofen will enhance posttraumatic regeneration after peripheral nerve injury.
  
  
  METHODS
  In adult female Wistar rats we introduced an experimental injury by excising a 5 mm piece of the tibial nerve and returning it to the injury site as an interpositional graft. The animals then received ibuprofen or phosphate buffered saline through an osmotic pump for a period of 3 weeks. Following the injury we recorded tibial functional index (TFI) on a weekly basis. After 3 months we measured nerve conduction velocity and peak amplitude of action potential (PAAP). Also, the histomorphometric analysis was carried out in the zone distal to the injury site.
  
  
  RESULTS
  We found that the animals receiving ibuprofen recovered the tibial nerve function more rapidly, with the TFI being significantly different 8, 9, 11 and 12 weeks after the injury. We also detected the values of the PAAP, the area of axons and the area of myelin to be significantly greater in the experimental group.
  
  
  CONCLUSIONS
  Our results show that ibuprofen significantly enhanced regeneration after tibial nerve axotomy and repair in rats. This study is expected to set a stage for testing the ibuprofen in the human patients.
authors.affiliation: Blond McIndoe Research Laboratories, The University of Manchester, Manchester Academic Health Science Centre, and Department of Plastic Surgery, University Hospital of South Manchester, Wythenshawe, Manchester, United Kingdom. tomas.madura@manchester.ac.uk
authors.forename: Tomas
authors.initials: T
authors.lastname: Madura
authors.forename: Koichi
authors.initials: K
authors.lastname: Tomita
authors.forename: Giorgio
authors.initials: G
authors.lastname: Terenghi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019771:Axotomy; D004594:Electrophysiology / Q000379:methods; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D009431:Neural Conduction; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D013979:Tibial Nerve / Q000502:physiology / Q000601:surgery*; D016896:Treatment Outcome; D020741:rho GTP-Binding Proteins / Q000187:drug effects* / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020741:rho GTP-Binding Proteins; D007052:Ibuprofen