**Abstract**

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 cytokines, 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.

**Keywords:** Schwann cell plasticity, dedifferentiated Schwann cells, peripheral nerve regeneration, myelin recovery

## **1. Introduction**

Schwann cells (SCs) are glial cells present in the peripheral nerve system (PNS). The name was given in honor of the German scientist Theodore Schwann, who discovered them in the nineteenth century [1] although they were not the main subject of his research. At that time it was thought that this type of cells is very complex and that the cells merge to supply peripheral nerves. Ramon y Cajal, only about 100 years later, discovered the true structure of the peripheral nerves, composed of axons and SCs that are in a symbiotic connection with it [2]. In the following years, with the evolution of electron microscopy, the study of SC morphology has developed continuously, leading to a better understanding of their complex biology.

It is known that nerves in PNS are much easier to regenerate than those in the central nervous system (CNS). Ramon y Cajal sensed very well that there is a "symbiosis" between the axon and the Schwann cells. Kidd et al. [3] described the Schwann cell as one of the largest and most complex cells in the body, which can develop and evolve rapidly after injury. The origin of the Schwann cell is in the

#### *Demyelination Disorders*

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.
