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Peripheral Nerve

Nervus periphericus

For medical students2 min readUpdated 2026-10-10

Peripheral nerves are complex anatomical structures that transmit nerve impulses, consisting of bundles of neuronal processes. The fibers within a nerve are organized by a multi-level connective tissue framework and supplied by their own vascular system for continuous nourishment.

"Matryoshka" principleThe connective tissue sheaths are hierarchically nested: the outer epineurium, the middle perineurium, and the inner endoneurium.
Vacuoles in cross-sectionThe clear optical halo around a nerve fiber in a histological slide is the space left by dissolved myelin lipids.
Mixed compositionA spinal nerve trunk contains both afferent (sensory) and efferent (motor) pathways.
Tissue trophic supplyBlood vessels supplying the nerve trunk, as well as clusters of adipocytes, are localized within the epineurium and perineurium.

General Architecture of a Nerve Trunk

On a transverse histological section, any nerve trunk appears as a collection of rounded fascicles enclosed within connective tissue layers. The basic structural components include:

Connective Tissue Framework

The architectonics of the sheaths follow a "matryoshka doll" principle. Moving from the outer surface inward, there are three organizational levels:

  1. Epineurium (Epineurium). The outermost and thickest layer, forming the external contour of the entire nerve. It is composed of dense fibrous connective tissue. It contains the largest nourishing blood vessels and clusters of adipocytes (fat cells).
  2. Perineurium (Perineurium). Intermediate layers of connective tissue that divide the main nerve trunk into separate, isolated fascicles of nerve fibers. Blood vessels and fat cells are also present here.
  3. Endoneurium (Endoneurium). The innermost and delicate layer, visible only at high magnification within the fascicles. The endoneurium lies between individual nerve fibers. Morphologically, it consists of extremely thin layers that stain oxyphilic (pink) due to the presence of collagen fibers. The primary cellular elements of the endoneurium are fibroblasts with characteristic spindle-shaped nuclei.

Microscopic Morphology of Nerve Fibers

When examining fascicles in a hematoxylin and eosin (H&E) stained slide, the predominant fiber type in a mixed nerve is myelinated. In the center of each such fiber lies the axon (axis cylinder), which appears as a darker structure.

Surrounding the axon, a clear, optically empty halo is visible—this is the myelin sheath. This clear appearance is due to histological sample preparation: lipids, which form the basis of myelin, dissolve in alcohols during tissue fixation, leaving an empty space behind.

Biological Nature of Neuronal Processes

Axons within a mixed nerve have different functional origins. They may represent one of four types of processes:

Based on myelination, the first three types are covered by well-developed sheaths, forming myelinated fibers. The fourth type (postganglionic sympathetic axons) comprises unmyelinated fibers. Their key feature is that a single Schwann cell envelops multiple axons simultaneously.

Spinal Roots and Nerve Formation

The formation of a spinal nerve is closely linked to the roots emerging in pairs from each spinal cord segment. Both roots contain myelinated nerve fibers.

Upon the fusion of the anterior and posterior roots, the spinal nerve trunk is formed. This junction is functionally mixed, as it contains both sensory and motor fibers.

Mnemonic

To remember the order of connective tissue sheaths from outermost to innermost, use the logic of Latin prefixes: EPI- (upon/around the entire nerve, outside) → PERI- (around an individual fascicle) → ENDO- (within the fascicle, between fibers).

Frequently asked questions

What forms the myelin sheath, and what are its functions?

The myelin sheath is formed by glial cells: Schwann cells (neurolemmocytes) in the peripheral nervous system, and oligodendrocytes in the CNS. Structurally, it is a multilayered system of tightly packed plasma membrane turns (elongated mesaxons) concentrically wrapped around the axon. Lipids predominate (~80%) over proteins (~20%).

Functions of the sheath:

  • Electrical insulation — acts as an effective dielectric, preventing nerve impulse dispersion.
  • Trophic support — participates in the nutrition of the axon.
  • Protective — shields the neuronal process from injury.
How do Schwann cells differ in myelinated versus unmyelinated fibers?

Schwann cells (neurolemmocytes) in myelinated and unmyelinated fibers differ in mesaxon structure, nuclear localization, and the number of enclosed processes.

FeatureIn myelinated fibersIn unmyelinated fibers
Nucleus locationPushed to the periphery along with the cytoplasmLocated centrally within the fiber
Number of axonsEncloses only a single axonMultiple (10–20) axons are embedded in the cytoplasm
MesaxonRepeatedly wrapped around the single axonShort, formed by simple depression/invagination
Why does the myelin sheath appear empty and clear in H&E stained slides?

Alcohols used during histological preparation completely dissolve the lipids that compose myelin, leaving a clear, unstained space where the sheath used to be.

Which cells form the connective tissue framework of the endoneurium?

The primary cellular elements of the deep endoneurial layers are fibroblasts. They are easily identified in micrographs by their characteristic spindle-shaped nuclei.

What is the functional difference between the anterior and posterior spinal roots?

The anterior root (Radix anterior) conducts efferent (motor) signals from the central nervous system to organs. The posterior root (Radix posterior) conducts afferent (sensory) signals and bears the spinal ganglion.

Are all fibers in a mixed nerve trunk covered with myelin?

No, not all. Most fibers are myelinated, but axons of sympathetic effector neurons (postganglionic fibers) are unmyelinated.

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