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Peripheral nerve regeneration in CNTF knockout mice
1Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, California 94305-5328, USA.
Objectives:
To determine the role of ciliary neurotrophic factor (CNTF) in the regeneration of the mouse sciatic nerve following injury by studying the CNTF knockout mouse in a blinded, randomized and controlled evaluation.
Study Design:
Fifty-eight wild-type and 57 CNTF knockout mice were randomly assigned to one of four treatment groups: sham surgery (sciatic nerve exposure), sciatic nerve crush, nerve transection without repair, and nerve transection followed by epineurial suture repair using 10-0 monofilament suture. Walking track analysis was performed before and after surgery at weekly intervals for 7 weeks, using a previously described formula. At the completion of walking track analysis, morphometric histological analysis of axon number and axon diameter in the distal sciatic nerves was performed.
Results:
The wild-type and knockout mice that underwent only sham surgery had no change in their walking tracks during the study interval (P = .30 on postoperative 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 similar levels of recovery after transection without repair (P = .78), and the rate of contracture formation was not significantly different (P = .40). The CNTF knockout and wild-type mice showed similar levels of recovery after epineurial repair (P>.31), however the rate of severe contractures was greater in the CNTF knockout mice (6 of 13) than in the wild-type mice (2 of 12) (P = .11).
Conclusion:
The absence of CNTF impairs the ability of mice to recover from 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 that CNTF is important for recovery of neuronal function following crush and transection nerve injuries.