Inhibition of inducible nitric oxide synthase promotes recovery of motor function in rats after sciatic nerve ischemia and reperfusion

Purpose: To investigate the effects of inhibition of inducible nitric oxide synthase (iNOS) on the recovery of motor function in the rat sciatic nerve after ischemia and reperfusion injury. Methods: A 10-mm segment of the sciatic nerve from 169 rats had 2 hours of ischemia followed by up to 42 days of reperfusion. The animals were divided into 2 groups that received either iNOS inhibitor 1400W or the same volume of sterile water subcutaneously. A walking track test was used to evaluate the motor functional recovery during reperfusion. Statistical analysis was performed for the measurements of the sciatic functional index (SFI) by using 2-way analysis of variance; 1-way analysis of variance was used for the post hoc analysis of specific values at each time point of the SFI measurement. Results: 1400W-treated rats had earlier motor functional recovery than controls, with a significantly improved SFI between days 11 and 28. Histology showed less axonal degeneration and earlier regeneration of nerve fibers in the 1400W group than in the controls. Inducible NOS messenger RNA and protein were up-regulated during the first 3 days of reperfusion but there was a down-regulation of neuronal NOS and up-regulation of endothelial NOS in control animals. 1400W treatment attenuated the increase of iNOS but had no effect on neuronal NOS and endothelial NOS. Conclusions: Our results indicate that early inhibition of iNOS appears to be critical for reducing or preventing ischemia and reperfusion injury.