Functional recovery after nerve repair with administration of TGF-b1&2 antibodies

Objective: Scar formation at a site of nerve injury can cause a mechanical barrier to axonal regeneration. We have evaluated the hypothesis that the application of a scar-preventing agent to a nerve repair site would permit enhanced regeneration. Method: The left sciatic nerve was exposed under general anaesthesia (Fentanyl/Fluanisone 0.8ml/kg & Midazolam 4mg/kg, i.p. Janissen/Roche) in 18 adult Sprague-Dawley rats. In 12 animals the nerve was sectioned and immediately re-approximated using 4 epineurial sutures, and in 6 of these neutralising antibodies to TGF- b1 & TGF- b2 (100 µg of each in 100 µl PBS, R & D systems) were injected into and around the proximal and distal nerve stumps. The 6 other animals acted as controls. After 7 weeks, again under anaesthesia, the extent of regeneration was assessed by determining the ratio of the compound action potential (CAP) modulus evoked by electrical stimulation of the nerve 2mm distal and 2mm proximal to the repair site. Results: After repair alone the median CAP ratio was 0.57, which was not significantly different from the controls (0.89). However, after administration of antibodies the median CAP ratio was significantly smaller than in controls (0.23, p<0.01, Mann-Whitney U test). The conduction velocity of axons that had regenerated across the repair site was significantly slower in both repair groups (repair median: 33.5m s-1, repair + antibodies: 32.6m s-1) than in controls (63.6 m s-1, p<0.01). Conclusions: We conclude that administration of scar-preventing antibodies, using this dosing regime, did not enhance regeneration of sectioned axons in the sciatic nerve. Supported by the Wellcome Trust.