Improved nerve regeneration with neutralization of transforming growth factor-β1

Objectives: Recovery of injured peripheral nerves depends on a balance between Schwann cell regeneration and scar formation. Transforming growth factor-beta 1 (TGF-beta 1) has been implicated as a humoral stimulus in scar formation. The neutralization of TGF-beta 1 has been beneficial in the reduction of fibrosis. This study was to identify the presence of TGF-beta 1 in regenerating peripheral nerve and to measure motor nerve regeneration by the neutralization of TGF-beta 1 in neural wounds. Study Design: A randomized study of rat sciatic nerve regeneration, Method Sciatic nerve axotomy was performed, followed by serial immunohistochemical staining by anti-TGF-beta 1 at 12 to 216 hours (n = 5). Two groups (n = 10) with sciatic axotomy and epineural repair were treated with a 7-day perineural administration of neutralizing antibody of TGF-beta 1 or saline carrier via subcutaneous silicone infusion port, A control group (n = 10) without axotomy with anti-TGF-beta 1 administration was established. At 12 weeks the compound muscle action potential amplitude (CMAP) and the muscle twitch strength generated by the gastrocnemius-soleus muscle complex were measured. Results: TGF-beta 1 was qualitatively present with maximal concentration by 72 to 144 hours. CMAP amplitude in the anti-TGF-beta 1/axotomy group was 49.6% of the control and the axotomy/saline group was 31% of the control. Muscle twitch strength was 74% and 46.5%, respectively. These differences were statistically significant, P =.05. Conclusions: The presence of TGF-beta 1 at regenerating nerve sites was confirmed. The benefit of neutralization of transforming growth factor on CMAP and muscle twitch strength was shown. These results suggest improved regeneration at nerve injury sites with neutralization of TGF-beta 1.