**2. Peripheral nerve injury**

What does peripheral nerve injury mean? This could mean a mechanical trauma, transection or crush, or a pathological condition, when could be affected sensory nerves, motor nerves or autonomic nerves. A peripheral neuropathy may affect one or many nerves, axon, or myelin in the first stage.

In the nerve transection, all nerve fibers are affected, while in a disease manifestation, only a number of nerve fibers are affected, others being normal (**Figures 2A** and **4**).

Very briefly, in peripheral neuropathies, it may be an axonal primary damage or a myelin sheath primary damage. After a period both components of the nerve fiber are affected.

Primary axonal degeneration, whether it is nerve transection or a pathological manifestation, is essentially the same: it starts with a Wallerian degeneration in the distal part of nerve (**Figure 1**), following the myelin destruction. On semithin transverse

#### **Figure 1.**

*Wallerian degeneration. After injury, axon and myelin sheath in the distal stump degenerate. Macrophages migrate to the site of lesion and with proliferating Schwann cells remove myelin debris. After the debris has been removed, dedifferentiated Schwann cells align forming bands of Bungner, guiding axonal sprout regeneration.*

*Schwann Cell Plasticity in Peripheral Nerve Regeneration after Injury DOI: http://dx.doi.org/10.5772/intechopen.91805*

#### **Figure 2.**

*Peripheral nerve pathological modifications (sural nerve biopsy): (A) a very mild affected nerve, with a normal fiber density; some myelinated fibers with small and medium mean diameter with demyelination; (B) a severe axonal destruction, with disappearance of many large diameter axons and with a low-fiber density; a degenerated axon is present; (C) many degenerated axons and demyelination present in the rest of myelinated fibers; (D) a very severe neuropathy with disappearance of most of the myelinated fibers; (E) some small myelinated axons with onion bulbs; (F) a hypermyelinated fiber in an HNPP case (tomacula) in the center of the image; (G) regeneration aspect: cluster of small axons (arrow). Semithin cross sections stained with toluidine blue; (under oil immersion – 60× Objective).*

sections (**Figure 2B** and **C**) and in electron microscopy images (**Figure 3**), the affected nerve fibers are seen to be in a process of necrobiosis. In electron microscopy images, autophagic vacuoles are seen, near the axon (**Figure 3A**) or in the exterior layer of SC,

#### **Figure 3.**

*Electron microscopy aspects of axonal degeneration (sural nerve biopsy). (A) A myelinated axon showing an autophagic vacuole between axon and myelin sheath. (B) A myelinated axon with an autophagic vacuole in the Schwann cell exterior cytoplasma: small myelin debris are seen. (C) The same aspect: an autophagic Schwann cell with many smaller or bigger fragments of myelin inside. (D) A macrophage with lipid droplets is present near myelinated axons. (E) Total myelin degradation; only irregular laminated structure is present, with no axon (cross sections; bar = 2 μm).*

under the basal lamina (**Figure 3B** and **C**) and macrophages (**Figure 3D**). After the destruction of the nerve fiber, only irregular structures of myelin residues can be seen (**Figure 3E**) or myelin debris like ovoids and balls (**Figure 4B** and **C**). If it is a chronic process, many nerve fibers disappear, the density of myelinated fibers being very low (**Figure 2D** and **E**). When the myelin is affected in the first step, not all Schwann cells are suffering in the same time. One internode with a very thin sheath between two normal internodes may be observed: segmental demyelination (**Figure 4A** and **B**). When a myelin protein, PMP22, is genetically affected, in hereditary neuropathy with pressure palsies (HNPP), the nerve biopsy shows demyelination and focal hypermyelination structures, tomacula (sausage-like) (**Figures 2F** and **4D**). In hypertrophic neuropathies, like Charcot-Marie-Tooth disease type 1A (CMT 1A) and chronic inflammatory demyelinating polyneuropathy (CIDP), some structures named "onion bulbs" are present, a result of concentric layers of Schwann cell processes and collagen around the axons (**Figure 2E**). It is a repetitive segmental demyelination and myelin regeneration.

*Schwann Cell Plasticity in Peripheral Nerve Regeneration after Injury DOI: http://dx.doi.org/10.5772/intechopen.91805*

#### **Figure 4.**

*Teased nerve fiber (sural nerve biopsy) panel. (A) A nerve fiber with segmental demyelination near two other normal myelinated fibers. (B) Near normal fibers, a fiber with segmental demyelination (a thin internode) and a fiber with few myelin ovoids and balls (axonal degeneration). (C) More myelin ovoids in an axonal degeneration. (D) A tomacula in myelin sheath of a nerve fiber.*

#### **Figure 5.**

*Peripheral nerve remyelination. In demyelinating peripheral neuropathies, the segmental demyelination is often seen. Following a Schwann cell degeneration, the lost myelin internode is replaced by some Schwann cells which generate myelin sheaths, resulting in many shorter internodes.*

After a segmental demyelination, along the affected internode, several Schwann cells arrive which begin to remyelinate this portion, the sign of remyelination being more short internodes (**Figure 5**).

The sign of axonal regeneration is observed on semithin sections and consists of the presence of some clusters of axons with the same small mean diameter and thinner myelin sheath (**Figure 2G**).

After these images sowing just few aspects of pathological degradation of peripheral nerve, focusing on myelin sheath damage, let's take a closer look at what happens in the Schwann cell, at the cellular and molecular level.
