Abstract

We continued our studies of ischemia-reperfusion (IR) injury, extending the reperfusion duration to 42 days to capture the fiber regeneration process. We used a rat model for IR injury produced by ligation and release of nooses around supplying vessels to the sciatic nerve. Fifty-six rats were used. One group (control N = 8) underwent sham ischemia; the other six groups (N = 8 each) underwent complete hind limb ischemia for 4 h followed by reperfusion durations of 0 h (ischemia alone), 3 h, 7 days, 14 days, 28 days, and 42 days. Behavioral and electrophysiological data were obtained immediately before euthanasia. Pathologically, three phases were identifiable: Phase 1 (0-3 h)-minimal pathological changes, minimal edema; phase 2 (7 days, 14 days)-prominent fiber degeneration, endoneurial edema; phase 3 (28 days, 42 days)-abundant small regenerating fiber clusters, minimal edema. Compound muscle action potential (CMAP) was the most sensitive index of neural deficits and recovery, showing progressive recovery beyond 14 days. Severe functional deficits developed immediately and persisted with a trend to recovery at the 42-day time-point. It was concluded that reperfusion, by oxidative injury, worsened nerve function and aggravated fiber degeneration, but in the longer time frame, permitted fiber regeneration to occur.