Ibuprofen improves functional outcome after axotomy and immediate repair in the peripheral nervous system.

摘要

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.