Peripheral nerves transmit signals between the central nervous system and the rest of the body. These delicate structures require robust protection, demanding a stable internal environment and physical resilience against movement and compression. This need for biochemical stability and mechanical support is met by three distinct layers of connective tissue that encase the nerve fibers. The composition of these sheaths—epineurium and perineurium being the focus—determines their unique protective roles.
The Organizational Hierarchy of a Peripheral Nerve
A peripheral nerve is organized in a hierarchical, cable-like fashion. The most basic unit is the axon, which is wrapped by a delicate, innermost layer. Groups of these individual nerve fibers are gathered into discrete bundles known as nerve fascicles. Multiple fascicles, which may carry signals to different destinations, are then combined to form the complete peripheral nerve trunk. The three connective tissue layers—epineurium, perineurium, and endoneurium—are named for their specific position relative to these groupings.
The Epineurium: Outer Mechanical Support
The epineurium is the outermost and thickest protective sheath, acting as the primary mechanical buffer for the entire nerve trunk. This tissue is classified as dense irregular connective tissue, characterized by densely packed collagen fibers arranged in a multi-directional, interwoven pattern. This irregular arrangement allows the nerve to withstand stresses from multiple directions, providing tensile strength and resistance to tearing.
The layer also contains adipose (fatty) tissue, which provides cushioning and acts as a shock absorber. The epineurium houses the vasa nervorum, the larger blood vessels that supply the nerve with oxygen and nutrients. A primary function is allowing for nerve movement, permitting the nerve to slide and stretch longitudinally as the body moves.
The Perineurium: The Specialized Nerve Barrier
The perineurium is the most specialized of the three sheaths, serving as a highly selective barrier. It is formed by concentric layers of flattened cells, known as perineurial cells, which create a sleeve around each nerve fascicle. The number of layers can vary significantly, from a single layer in smaller nerves up to 16 layers in larger nerve trunks.
These perineurial cells are histologically unique, often described as epithelioid myofibroblasts because they possess characteristics of both epithelial and contractile cells. Their epithelial-like function is established by continuous tight junctions between adjacent cells, which fuse the cell membranes and restrict the passage of substances. This cellular architecture forms the basis of the perineurial barrier, a component of the larger Blood-Nerve Barrier (BNB).
The tight junctions create a diffusion barrier, preventing harmful macromolecules, pathogens, and unwanted ions from entering the delicate internal nerve microenvironment. This protection maintains the precise chemical and ionic balance required for axons to transmit electrical signals effectively. The myofibroblast properties of the cells, including their ability to contract, also contribute to maintaining a slightly elevated fluid pressure within the fascicle, which is necessary for axonal health.
The Endoneurium: Support for Individual Axons
The endoneurium is the innermost connective tissue layer, directly surrounding each individual axon and its associated Schwann cell sheath. It is composed of a delicate mesh of loose connective tissue, primarily fine collagen fibers (Type III) embedded within a fluid-filled matrix. This loose arrangement creates a soft, supportive scaffold for the fragile nerve fibers.
This layer contains endoneurial fluid, a low-protein liquid that helps maintain the microenvironment necessary for nerve impulse conduction. The endoneurium also supports a network of capillaries for nutrient delivery to the axons and Schwann cells. Its primary role is to preserve the microenvironment and provide structural support for the individual nerve fibers.