Improved nerve regeneration with neutralization of transforming growth factor-beta1.

OBJECTIVES

Recovery of injured peripheral nerves depends on a balance between Schwann cell regeneration and scar formation. Transforming growth factor-beta1 (TGF-beta1) has been implicated as a humoral stimulus in scar formation. The neutralization of TGF-beta1 has been beneficial in the reduction of fibrosis. This study was to identify the presence of TGF-beta1 in regenerating peripheral nerve and to measure motor nerve regeneration by the neutralization of TGF-beta1 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-beta1 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-beta1 or saline carrier via subcutaneous silicone infusion port. A control group (n = 10) without axotomy with anti-TGF-beta1 administration was established. At 12 weeks the compound muscle action potential amplitude (CMAP) and the muscle twitch strength generated by the gastrocnemiussoleus muscle complex were measured.

RESULTS

TGF-beta1 was qualitatively present with maximal concentration by 72 to 144 hours. CMAP amplitude in the anti-TGF-beta1/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-beta1 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-beta1.