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Effects of hyperbaric oxygen treatment (HBO) on nerve regeneration in acellular nerve and muscle grafts were investigated in rats. Nerve and muscle grafts were made acellular by freeze-thawing and the obtained grafts were used to bridge a 10-mm gap in the sciatic nerve on the left and right sides, respectively. Rats were treated with HBO (100% oxygen for 90 minutes at 2.5 atmospheres absolute pressure ATA) twice a day for 7 days. Axonal outgrowth, Schwann cell migration and invasion of macrophages were examined 10 days after the graft procedure by staining neurofilaments, S-100 proteins and the macrophage antibodies ED1 and ED2, respectively. Axonal outgrowth and Schwann cell migration in acellular nerve grafts were superior to that found in the acellular muscle grafts. However, there was no difference between HBO-treated and non-treated rats in acellular nerve grafts. Such a difference was found in acellular muscle grafts concerning both axonal outgrowth and Schwann cell migration from the proximal nerve end. No differences in the content of macrophages or neovascularization (alkaline phosphatase staining) in either of the grafts and treatments were seen. It is concluded that there is a differential effect of HBO-treatment in acellular nerve and muscle grafts and that HBO-treatment has no effect on the regeneration process in acellular nerve grafts, in contrast to fresh cellular nerve grafts where a beneficial effect has previously been reported.