Free radical damage in acute nerve compression

Nerve compression causes injury by local ischemia and direct mechanical distortion. Peripheral nerves in diabetes mellitus are more prone to injury than those of nondiabetics. We sought to determine whether reperfusion- induced, oxygen-derived free radical injury occurs in peripheral nerves subjected to acute compression in normal and chronically diabetic rats. Female Sprague-Dawley rats weighing 250 to 275 g (N = 347) were divided into two groups: normal and streptozocin-induced diabetics. A total of 187 normal and 160 diabetic nerves were analyzed. After 8 weeks of untreated hyperglycemia, the sciatic nerves of normal and diabetes mellitus rats were subjected to one of three operations: a sham operation, 24-hour compression alone, and 24-hour compression followed by 1-hour reperfusion (CR). Nerve compression was established by banding the right sciatic nerve with a Silastic tubing, 1 cm long and 0.62 mm internal diameter, which was secured with 6-0 nylon suture. In the CR group, after 24 hours of compression, the tubings were released for 1 hour to permit reperfusion. Nerve tissue within the zone of compression underwent biopsy examination and was frozen for subsequent analysis. Blood flow to the nerve was quantified by injecting fluorescein (10 mg/kg intravenously) 10 minutes before harvest and measuring tissue levels fluommetrically. Compression with the Silastic tubing significantly reduced neural blood flow by 75%. Blood flow improved but failed to return to baseline levels after tubing release in diabetes mellitus nerves while perfusion returned to baseline in non-diabetes mellitus nerves. Nerve homogenate was assayed for malonyldialdehyde, an indicator of lipoperoxidation, as well as enzymes of cellular defense and glucose metabolism. Antioxidants, deferoxamine and lazaroid U74389F, were given at various time intervals in an attempt to reduce oxidative injury. Malonyldialdehyde levels rose significantly after reperfusion: a 310% increase from baseline in diabetes mellitus nerves (p < 0.01) and a 147% increase in non-diabetes mellitus nerves (p < 0.05). Enzymes of cellular defense and glucose metabolism increased activity during nerve compression (ischemia). While activities remained elevated or increased in non-diabetes mellitus nerves after reperfusion, enzyme activities in diabetes mellitus nerves tended to decline, suggesting an inability of diabetes mellitus nerves to tolerate reperfusion-induced metabolic stress. Both deferoxamine and lazamid U74389F significantly reduced malonyldialdehyde levels from those of untreated controls in reperfused diabetes mellitus nerves. We conclude that incomplete ischemia was created in this experimental model and peripheral nerves were susceptible to free radical damage as reflected by increased lipid peroxidation and decreased antioxidant defenses. Diabetic nerves were more susceptible to free radical damage than non-diabetes mellitus nerves.