Peripheral nerve regeneration in CNTF knockout mice

Objectives: To determine the role of ciliary neurotrophic factor (CNTF) in the regeneration of the mouse sciatic nerve following injury by studying th e CNTF knockout mouse in a blinded, randomized and controlled evaluation, S tudy Design: Fifty-eight wildtype and 57 CNTF knockout mice were randomly a ssigned to one of four treatment groups: sham surgery (sciatic nerve exposu re), sciatic nerve crush, nerve transection without repair, and nerve trans ection followed by epineurial suture repair using 10-0 monofilament suture, Walking track analysis was performed before and after surgery at weekly in tervals for 7 weeks, using a previously described formula. At the completio n of walking track analysis, morphometric histological analysis of axon num ber and axon diameter in the distal sciatic nerves was performed. Results: The wild-type and knockout mice that underwent only sham surgery had no cha nge in their walking tracks during the study interval (P = .30 on postopera tive day 49). The wild-type mice that underwent sciatic nerve crush showed complete functional recovery (P =.66 on postoperative day 28), but the CNTF knockout mice whose sciatic nerves were crushed did not fully recover (P = .05 on postoperative day 49), The CNTF knockout and wild-type mice showed s imilar levels of recovery after transection without repair (P =.78), and th e rate of contracture formation was not significantly different (P =.40). T he CNTF knockout and wild-type mice showed similar levels of recovery after epineurial repair (P >.31), however the rate of severe contractures was gr eater in the CNTF knockout mice (6 of 13) than in the wildtype mice (2 of 1 2) (P =.11). Conclusion: The absence of CNTF impairs the ability of mice to recover fi om a sciatic nerve crush injury, There is also a trend toward a greater rate of contracture formation after sciatic nerve transection and epineurial suture repair when CNTF is unavailable. These findings suggest t hat CNTF is important for recovery of neuronal function following crush and transection nerve injuries.