Trapidil, an antianginal drug with inhibitory effects on platelet-derived growth factor (PDGF), has been shown to reduce reactive fibrosis in models of central nervous system injury. Therefore, we evaluated trapidil's effects on fibroblast activity, Schwann cell proliferation, and PDGF receptor levels in rats after transection and anastomosis of the sciatic nerve. We also evaluated the effect of Schwann cell proliferation on regeneration of anastomosed sciatic nerves.
Wistar rats were randomly divided into 3 groups. Group 1 (N=10) was used to determine normal peripheral nerve morphology (via light and electron microscopy) and PDGF receptor levels. Group 2 (N=20) underwent sciatic nerve anastomosis after nerve transection to examine the influence of the surgical procedure on PDGF receptor levels and the microscopic findings. Group 3 (20 rats) received a single intraperitoneal dose of trapidil (40 mg/kg) immediately after the surgical procedure to investigate its effects on fibroblast activity, Schwann cell proliferation, and PDGF levels.
PDGF-A and PDGF-B receptor levels were lower in group 3, the trapidil-treated group, than group 2 on all posttransection days examined. Ultrastructural analysis revealed that group 3 also had lower levels of fibroblast activity and Schwann cell proliferation than group 2. However, the peripheral nerve ultrastructure and degree of axonal regeneration were similar between groups 2 and 3 at 14 days posttransection.
Trapidil treatment significantly decreased reactive fibrosis and PDGF receptor expression after peripheral nerve injury, and thus, may be useful therapeutically. These results also suggest that Schwann cells alone are not effective in promoting neurite formation.