Effects of Inducible NOS Inhibition on Motor Function Recovery After Sciatic Nerve Ischemia and Reperfusion in Rats

Abstract

Purpose: Introduction: Nitric oxide (NO) is known to play an important role in ischemia and reperfusion (I/R) injuries in the peripheral nerve. However, among various NO synthases (NOS), the effects of inducible NOS (iNOS) on peripheral nerve I/R injuries are still under debate. This study presents the influence of iNOS on the regeneration of crushed peripheral nerve in rats.

Materials and Methods: One hundred and seventy female Sprague-Dawley rats (body weights 175-200 g) were randomly divided into two groups to receive an injection of 1400W (iNOS specific inhibitor, 3 mg/kg) or the same volume of purified water. One sciatic nerve of each rat (10 mm in length) was subjected of a 100-g crush load for 2 hours to induce ischemia. Motor functional recovery by walking track test and histology of the crushed nerve in the two groups were evaluated at different reperfusion time (3 hours, and 1, 3, 7, 11, 14, 21, 28, 35, and 42 days). mRNA and protein levels for iNOS in the nerve were measured.

Results: Sciatic functional index (SFI) for motor functional recovery in the 1400W treated group improved at a significantly faster rate than that in the control group from day 11 after the ischemia. The difference peaked at day 18 (-46.8 in the 1400W treated group and -29.4 in the control group) and lasted until day 28. Histologic results were comparable with motor functional results. Histological observation revealed less axonal degeneration and earlier regeneration of nerve fibers in the 1400W treated rats than in the control rats. iNOS mRNA and protein were upregulated during the first 3 days of reperfusion, and iNOS inhibitor significantly attenuated the increased iNOS during the early phase of the reperfusion until 7days.

Conclusion: Inhibition of iNOS during the regeneration of the ischemic nerve influenced mRNA and protein level early in the reperfused period and assured faster functional recovery faster than in the untreated group. These results suggest that early administration of 1400W has therapeutic potential for the treatment of I/R injury.