The initial period of peripheral nerve regeneration and the importance of the local environment for the conditioning lesion effect

The aim of this study was to investigate the early period of neurite outgrowth in the regenerating rat sciatic nerve and to determine if the non-neuronal cells were important for the conditioning lesion effect. Regeneration distance was evaluated with the pinch-reflex test 6 h to 5 days after a test crush lesion. The regeneration velocity accelerated during approximately 3 days, whereupon outgrowth continued with a constant velocity. In unconditioned nerves the initial delay was 2.8 h and the constant rate of regeneration was 3.2 mm/day. In nerves with a distal conditioning lesion the initial delay was 2.4 h and the rate of regeneration increased by 52%. When the test crush was applied at the same place as the conditioning crush the initial delay was 1.9 h and the rate of regeneration increased by 61%. The conditioning lesion effect was not influenced by the distance between the cell body and the conditioning crush lesion. Furthermore, the conditioning lesion effect could not be expressed if conditioned axons grew into a freeze injured nerve section. Incorporation of 3H]thymidine increased in the regenerating nerve segment. The increase occurred earlier if this segment had been subjected to a conditioning crush lesion. The results of these experiments showed that peripheral neurites start to regenerate within a few hours after an injury, suggesting that growth cone formation is independent of the cell body reaction. A conditioning crush lesion increases the regeneration velocity and its acceleration, and the conditioning lesion effect cannot be expressed in the absence of living Schwann and other non-neuronal cells.