Figure 1.

Diagram of Schwann cell response to nerve injury. (1) Schematic representation of a single neuron with myelinating SCs and resident macrophages. For simplification, the basal lamina around SCs is not shown. (2) After injury, the nerve distal to the injury site degenerates and undergoes a series of complex multicellular and molecular events in which SCs play a role of orchestrator. SCs transdifferentiate into repair-promoting cells, creating a permissive and favorable environment for nerve regeneration. SCs downregulate pro-myelinating genes and clear their myelin sheaths. They proliferate, secrete several pro-inflammatory cytokines and trophic factors that support glial and neuronal survival and regrowth. Axonal and myelin debris are also phagocyted by resident and blood-derived macrophages recruited by SCs. SCs interact with fibroblasts to build a bridge between the two stumps of the nerve over the lesion site. (3) Newly formed vasculature guides the SCs and the growing axons through the lesion site. In the distal stump, SCs align in tracts named bands of Büngner to provide a trophic and physical support for axons to regrow. (4) After axonal regeneration, transdifferentiated SCs readily exit the cell cycle, differentiate again and remyelinate the axons to support the complete functional recovery. However, the newly-formed myelin sheaths are most of the time shorter and thinner than expected based on axonal diameter. Specialized terminal SCs direct reinnervation by helping the axons to find their paths toward their initial targets. (5) Diagram displaying the various roles played by a transdifferentiated SC to create a favorable environment for nerve repair.