Methods: To mimic I/R injury, a 10 mm segment of the sciatic nerve in 146 rats was subjected to 100 g compression load for a 2-hour duration. A pilot study was performed in 21 rats to determine dose (3mg/kg or 10mg/kg) and duration (day 0, 1, 3, 7, and 14 consecutive days, twice a day) reactions of 1400W on motor functional recovery of reperfused nerve. The remaining animals were divided into two groups; one group received 1400W, the other group received the same volume of water subcutaneously. Walking track test and histological examination were performed at intervals up to 42 days after crush. Sciatic functional index (SFI) was measured to indicate motor function (0 indicates normal nerve function and -100 represents complete dysfunction).

Results: The pilot study showed that the time course of motor functional recovery was no significant different between low dose (3 mg/kg 1400W) and high dose (10 mg/kg) and between the durations of 1400W administration from only one bonus administration to consecutive administration of 14 days. Accordingly, a dosage of 3 mg/kg 1400W and duration of one day were selected to perform the functional study. Rats in the 1400W group had earlier motor functional recovery than those in controls, with significantly (p<0.05 to < 0.01) improved SFI between days 11 and 28. Histology revealed less axonal degeneration and earlier regeneration of nerve fibers in the 1400W group than in controls. Real-time PCR technique showed that the expression of iNOS mRNA in controls was significantly upregulated from normal at 3h, 24h, and 3 days of reperfusion, but was significantly downregulated following 1400W administration. At 7 days of reperfusion, iNOS mRNA expression was lowered in controls, with no significant difference between the two groups.

Conclusion: 1400W treatment effectively promotes motor functional recovery in rat sciatic nerve following I/R injury. This accelerated rate of recovery in 1400W-treated animals may be due to inhibition of iNOS by 1400W. Increased NO production from iNOS appears to be detrimental in nerve degeneration and regeneration because iNOS can adversely affect many biological activities, thereby leading to cellular necrosis. Our results support a NO-involved mechanism in I/R injury and indicate that inhibition of iNOS has potential clinical benefit in treating I/R injury in the peripheral nerve.