The use of ciliary neurotrophic factor to promote recovery after peripheral nerve injury by delivering it at the site of the cell body

摘要

Despite a body of evidence showing that various neurotrophic factors support the survival of nerve cells and stimulate axonal outgrowth, doubt remains about their optimal site of application as well as the more compelling question of what clinical benefit, if any, they would confer. Ciliary neurotrophic factor (CNTF) supports the survival of motorneurons in vitro and in vivo. Direct delivery of CNTF to the cell bodies may help reduce the side effects and overcome the problem of rapid systemic clearance. The aim of this study was to establish whether nerve regeneration may be improved upon by the controlled addition of a specific humoral neurotrophic substance (CNTF) at the level of the cell body. Three groups of five adult sheep were used. The first group acted as normal controls. In the second and third groups, the median nerve was divided and repaired using an epineurial suture technique. In the second group, CNTF was supplied into the CSF at the level of C6 by an implanted osmotic pump. In the third group physiological saline was placed in the osmotic pump. The animals underwent comprehensive electrophysiological and isometric tension experiments at six months. All of the animals had reduced electrophysiological, morphometric and isometric tension indices after surgery compared to normal. The CNTF group had better results than the saline group in the following; (1) area and amplitude of the muscle action potential (2) the percentage of tetanus and muscle mass preserved after repair. These differences were only statistically significant for amplitude of the muscle action potential. No statistical difference was found in the morphological indices (fibre diameter, axon diameter, myelin thickness and internodal length) between the CNTF and saline groups. CNTF does not confer a functional benefit when applied at the level of the cell body.