OBSERVATIONS ON THE BLOOD AND PERINEURIAL PERMEABILITY BARRIERS OF SURVIVING NERVE ALLOGRAFTS IN IMMUNODEFICIENT AND IMMUNOSUPPRESSED RATS

The authors investigate whether there are any permeability changes in the endoneurial blood-nerve barrier and the perineurium-nerve barrier of surviving nerve allografts. In a normal nerve. the blood-nerve barr ier regulates the passage of substances from endoneurial blood vessels into the endoneurium, whereas the perineurium-nerve barrier protects the endoneurium from agents that escape from permeable epineurial vess els and accumulate around the nerve. Nerves from ACI rats were transpl anted into immunologically deficient nude rats or normal Fischer rats immunosuppressed with cyclosporin A. None of the nerve allografts was rejected. The blood-nerve barrier of nerve allografts at 2 and 6 weeks postoperatively was permeable to intravenously injected horseradish p eroxidase, which spread into endoneurial tissue. Electron microscopy r evealed that horseradish peroxidase escaped from endoneurial vessels t hrough intercellular junctions between endothelial cells. At 24 weeks, the blood-nerve barrier of nerve allografts had recovered and the end oneurial vessels, like those in normal nerves, were impermeable to hor seradish peroxidase. The perineurium-nerve barrier of nerve allografts remained impermeable to horseradish peroxidase at all times. Axons we re grouped into numerous minifascicles at nerve anastomosis zones at 2 4 weeks. Each nerve fascicle was surrounded by an impermeable perineur ium. These results demonstrate that regenerated axons in long-term sur viving nerve allografts and at anastomosis zones are protected by perm eability barriers. It is concluded that permeability barriers of nerve allografts are not permanently altered by a foreign environment (graf ts to nude rats) even when immunosuppression with cyclosporin A is req uired to prevent allograft rejection (grafts to Fischer rats).