Local application of olprinone for promotion of peripheral nerve regeneration.

Abstract

Olprinone was applied locally to the sciatic nerves of rats, and nerve regeneration activity was examined in relation to heat shock protein (HSP)27 expression. Adult rat sciatic nerves were locally exposed to olprinone, physiological saline, or a mixture of saline and HCl and underwent crush injury. HSP27 protein levels were assessed by Western blotting and immunohistochemistry. Nerve regeneration was assessed by sciatic function index (SFI) and by morphological evaluation. Olprinone was detected in ipsilateral L4-L6 dorsal root ganglion (DRG) and sciatic nerve proximal to the site of crush injury. Western blot analysis of the DRG 24 h postsurgery and the sciatic nerve 7 days postsurgery showed a marked increase in HSP27 protein levels in the olprinone-treated group. Immunohistochemical analysis was consistent with the Western blot analysis. SFI was significantly better for the olprinone-treated group than for either the saline- or HCl-treated groups at 7, 22, and 25 days, respectively, after application. The packing density and the number of myelinated axons 21 days after the crush injury in the olprinone-treated group were significantly greater in comparison to the other groups. The local application of olprinone to the sciatic nerve increases HSP27 protein levels in DRG in the early stage and in the sciatic nerve 1 week thereafter. The results from this crush model indicate that increasing levels of HSP27 appear to result in therapeutic effects.