The autophagic role of Schwann cell on regeneration of rat sciatic nerves

Background: The removal of degenerated debris of myelin sheath during wallerian degeneration is very important for nerve regeneration, but the mechanism by which the debris is removed has not been completely clarified and there is still considerable controversies on the types of cells involved in the clearance process. Objective: To investigate the autophagic role of Schwann cell on regeneration of rat sciatic nerves. Design: Completely randomized animal experiment conducted in March 2003. Setting and participants: Rats were bought from the Laboratory Animal Service Center of The First Military Medical University. Totally 30 adult Wistar rats were used, 15 males and 15 females, weighing 180-250 g. Intervention: Wallerian degeneration model was made by transecting the rat sciatic nerve. Samples from the distal stump were obtained 0, 0.5, 1, 1.5, 2, 3, 4, 5, 7, 10, 15 days after transaction, respectively, and ultrathin sections were prepared for examination with electron microscope. Main outcome measures: Ultrastructure of axon and myelin sheath were observed under electron microscope. Acid phosphatase(AcPase) activity was detected after Gomori staining. Results: Axons start to separate from myelin sheath at day 0.5 after transection and degenerated quickly while displaying vacuole appearance. From day 2 onwards, myelin sheath creased and broke into fragments, large membrane-bound myelin debris and many other small scattered ones appeared in Schwann cells and fused with lysosomes to form ACPase reaction-positive autophagic vacuoles. Young cells were seen by chance at endoneural space and many of them appeared a week later. From day 7 onwards the number of autophagic vacuoles began to diminish. Macrophages were incidentally found all the time with autophagic vacuoles in it. Conclusion: The degenerating myelin debris were cleared mainly by autophagy of Schwann cells during regeneration of rat sciatic nerve. Schwann cells dedifferentiated to Schwann cell precursors, then proliferated and differentiated vastly to take part in the regeneration of nerves.