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BACKGROUND Constriction of the sciatic nerve by loose ligation produces an inflammatory neuropathic injury. This represents an animal model for peripheral mononeuropathy. Oxygen-derived free radicals are suspected to play an important role in the pathogenesis of ischemia/reperfusion injury, leading to neurogenic inflammation. Hyperbaric oxygen (HBO) has been used anecdotally to treat clinically similar conditions in humans, but specific effects on the animal model have not been well studied. OBJECTIVE This study in a rat model examined the effects of hyperbaric oxygen on skin blood flow and tissue morphology by light and electron microscopy following sciatic nerve constriction. DESIGN A scientific investigation in a rat model. METHODS In this study, the neuropathic injury was established by loose ligation of the rat sciatic nerve. The animals were divided into three groups, sham (S, n=8), ligation but no treatment (LN, n=8) and ligation and treatment with hyperbaric oxygen (LT, n=8). The treatment group (n=8) received hyperbaric oxygen treatment immediately following the injury and daily for four additional days at the same time interval. One hundred percent O2 at 3 atmospheres absolute pressure (66 feet sea water) was administered for two hours. The hindpaws of the rats were observed by light microscopy, electron microscopy, laser Doppler flowmetry (LDF), and clinically for the presence of edema. RESULTS Untreated animals demonstrated marked tissue edema following sciatic constriction, whereas animals that received hyperbaric oxygen had minimal to no edema. The sham group demonstrated normal histology. The group not treated with hyperbaric oxygen demonstrated swollen mitochondria (2-3 times), with loss of cellular integrity, multiple vacuole formation in both nerve and muscle tissue, widened sarcomeres in muscle, and degenerative changes in the nerve myelin sheaths. The group treated with hyperbaric oxygen demonstrated preservation of cellular structure including mitochondrial integrity, no vacuole formation, and maintenance of normal, easily identifiable nerve structure. The sham group had no change of skin blood flow. Skin blood flow of LT group was decreased immediately after ligation (p