FREE-RADICAL DAMAGE IN ACUTE NERVE COMPRESSION

Nerve compression causes injury by local ischemia and direct mechanica l distortion. Peripheral nerves in diabetes mellitus are more prone to injury than those of nondiabetics. We sought to determine whether rep erfusion-induced, oxygen-derived free radical injury occurs in periphe ral nerves subjected to acute compression in normal and chronically di abetic rats. Female Sprague-Dawley rats weighing 250 to 275 g (N = 347 ) were divided into two groups: normal and streptozocin-induced diabet ics. A total of 187 normal and 160 diabetic nerves were analyzed. Afte r 8 weeks of untreated hyperglycemia, the sciatic nerves of normal and diabetes mellitus rats were subjected to one of three operations: a s ham operation, 24-hour compression alone, and 24-hour compression foll owed 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 release d for 1 hour to permit reperfusion. Nerve tissue within the zone of co mpression underwent biopsy examination and was frozen for subsequent a nalysis. Blood flow to the nerve was quantified by injecting fluoresce in (10 mg/kg intravenously) 10 minutes before harvest and measuring ti ssue levels fluorometrically. Compression with the Silastic tubing sig nificantly reduced neural blood flow by 75%. Blood flow improved but f ailed to return to baseline levels after tubing release in diabetes me llitus nerves while perfusion returned to baseline in non-diabetes mel litus nerves. Nerve homogenate was assayed for malonyldialdehyde, an i ndicator of lipoperoxidation, as well as enzymes of cellular defense a nd glucose metabolism. Antioxidants, deferoxamine and lazaroid U74389F , were given at various time intervals in an attempt to reduce oxidati ve injury. Malonyldialdehyde levels rose significantly after reperfusi on: a 310% increase from baseline in diabetes mellitus nerves (p < 0.0 1) and a 147% increase in non-diabetes mellitus nerves (p < 0.05). Enz ymes of cellular defense and glucose metabolism increased activity dur ing nerve compression (ischemia). While activities remained elevated o r increased in non-diabetes mellitus nerves after reperfusion, enzyme activities in diabetes mellitus nerves tended to decline, suggesting a n inability of diabetes mellitus nerves to tolerate reperfusion-induce d metabolic stress. Both deferoxamine and lazaroid U74389F significant ly reduced malonyldialdehyde levels from those of untreated controls i n reperfused diabetes mellitus nerves. We conclude that incomplete isc hemia was created in this experimental model and peripheral nerves wer e susceptible to free radical damage as reflected by increased lipid p eroxidation and decreased antioxidant defenses. Diabetic nerves were m ore susceptible to free radical damage than non-diabetes mellitus nerv es.