Host nerve fibers that regenerate and reside long-term in a rejected nerve allograft are not protected by permability barriers.

We investigated whether permeability barriers develop and protect host nerve fibers that regenerate and reside long-term in a rejected nerve allograft. In order for the barriers to form, host cells have to enter the rejected allograft and differentiate into new endothelial and perineurial cells that respectively form the impermeable endoneurial blood-nerve and the perineurium-nerve barriers that are present in normal nerve. A 2-cm long graft of peroneal nerve was taken from American Cancer Institute (ACI) or Fischer (FR) rats and transplanted to bridge a 2-cm gap between the cut ends of the peroneal nerve of other FR rats. Six months postoperatively, histology revealed that regenerated host nerve fibers in ACI allografts were compartmentalized into numerous minifascicles by perineurial cells and that blood vessels were located outside rather than inside the perineurial compartments among the nerve fibers. Administration of the permeability indicator horseradish peroxidase to allograft recipients (intravenously or topically to the graft in situ) revealed that it entered the endoneurium of microcompartments and spread around the nerve fibers. In contrast, none of the indicator reached nerve fibers in FR syngrafts or normal ACI or FR nerves which were not microcompartmentalized. We concluded that host nerve fibers that regenerate and reside long-term in a rejected nerve allograft are not protected by permeability barriers.