The effects of allopurinol on the functional recovery of rats subject to sciatic nerve contusion
Xanthine oxidase free radicals are important mediators of injury following ischemia. Their effects can be inhibited by allopurinol - a competitive inhibitor of xanthine oxidase. The object of this study was to determine if the administration of allopurinol could reduce the functional deficit or improve the functional recovery of peripheral nerves subject to an acute crush injury. Two experiments were carried out. In each, twenty-four outbred male Sprague-Dawley rats, were randomly allocated to three groups: (1) sham operated group - sciatic nerve exposure only, (2) sciatic nerve contusion without active pre-treatment, (3) sciatic nerve contusion with intra-peritoneal injections of allopurinol (20 mg/kg), 24 hours and 1 hour pre-operatively. The two experiments differed in the force used to contuse the nerve. In the first experiment, a 0.98 N crush was applied for 10 minutes, while in the second experiment 147 N crush was applied for 10 minutes. Functional assessments were made by allowing the rats to walk down a confined walkway with moistened hind paws, leaving hind paw prints on photo-copying paper impregnated with bromphenol blue. The paper was coded by animal number and measurements were made to calculate the Sciatic Functional Index (SFI). Rats subjected to sham operations exhibited no functional deficit, while rats subjected to sciatic nerve contusion had obvious functional deficits with longer, narrower hind paw prints on the affected side. The time for recovery from 0.98 N crush (11 days) was shorter than that for 147 N of crush (60 days). In the 0.98 N crush experiment there were no significant differences between the time courses of recovery for the allopurinol treated and untreated animals. In the 147 N crush experiment there was little difference between the two groups until 60 days post-operatively, when the allopurinol pre-treated group were slightly less disabled than the control group. These results confirm that mechanical trauma is the major determinant of functional impairment. Xanthine oxidase-mediated free radical damage do not play a significant role in acutely contused peripheral nerves.
Murrell, GAC; Davies, H; Seaber, AV; Goldner, RD; Chen, LE
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