Wallerian degeneration

The distal nerve plays a crucial role in axonal regeneration since it exhibits various morphological and molecular changes required for axonal regrowth of peripheral but also of usually non-regenerating central nerve fibers into peripheral nerve segments (Stoll et al., 1989). This ‘Wallerian degeneration’ leads to the removal and recycling of axons as well as of their myelin sheaths within a few days after lesion. Schwann cells and invading macrophages eliminate cell remnants and other growth-inhibiting substances. Schwann cells are then transformed into an undifferentiated, non-myelinating phenotype and divide with a maximum at day three after lesion. Their proliferation and migration is required for the formation of endoneural tubes (bands of Buengner) which provide the adhesive substrate for regenerating axons. Therefore, Schwann cells – in contrast to astrocytes or fibroblasts – are able to promote axonal growth of central and peripheral neurons at least for some time. However, an important restraint on long-distance axonal regeneration results from the reduced proliferation rate of Schwann cells observed along the lesioned nerve with increasing distance from the site of injury. The impaired glial reaction may in part be due to the decreased number of invading macrophages. They are required for complete myelin clearance in vivo (Lunn et al., 1989) and produce a conditioned medium that is mitogenic for Schwann cells after myelin phagocytosis in vitro (Baichwal et al., 1988).