In the normal peripheral nervous system, Schwann cells (SCs) are present in two different states of differentiation: myelinating SCs that surround large-caliber axons, forming myelin sheath, and non-myelinating SCs that surround more small-caliber axons forming Remak bundles. Under pathological conditions (injury or inflammation), SCs, with a remarkable plasticity, undergo phenotypic transformations, downregulating the production of myelin proteins mRNAs, upregulating neurotrophic factors and

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... tokines, thus promoting the axonal regeneration. Dedifferentiated SCs activate the protein degradation, participating in the demyelination process and clearance of myelin debris; attract macrophages helping wound healing; proliferate to replace lost cells; guide axonal growth; and protect against secondary axonal damage. Thus, SC functions have a critical contribution to regeneration processes that occur in peripheral nerve after injury. Schwann Cells 2 neural crest, and this differentiation is made by the regulation of Sox10 but also in the presence of Notch and endothelin signaling [4, 5]. After a peripheral nerve lesion, a series of cellular changes occur at both axons and Schwann cells, a phenomenon known as Wallerian degeneration: axonal degeneration and myelin destruction, followed by a dedifferentiation (an immature-like phenotype of SCs) and proliferation of Schwann cells [6]. The purpose of this chapter is to highlight the extremely important role of the Schwann cell in the regeneration of the peripheral nerve and its extraordinary plasticity in order to ensure this phenomenon.