Epineurium

Epineurium is the outermost connective tissue sheath of a peripheral nerve. It encloses the entire nerve, including its internal fascicles and the blood vessels and lymphatics that supply it. The epineurium is composed mainly of dense irregular connective tissue and is rich in collagen fibers, with occasional elastic fibers and resident fibroblasts. It may also contain adipose tissue, particularly in larger nerves.

Within the epineurium run the vasa nervorum, small arteries, veins, and lymphatics that provide the nerve with nutrients and remove waste. The epineurium also contains connective tissue septa that partition the nerve into fascicles, though each fascicle is primarily wrapped by its own perineurium while the epineurium surrounds several fascicles as a whole.

Functionally, the epineurium guards the nerve against mechanical injury, distributes and absorbs mechanical stresses, and contributes to the nerve's elasticity. It also acts as a conduit for the nerve’s blood supply and serves as a diffusion matrix for nutrients to deeper layers such as the endoneurium and perineurium.

In development, the epineurium is derived from mesenchyme and is distinct from the endoneurium, which surrounds individual axons, and the perineurium, which envelops each fascicle. Clinically, injury to the epineurium can accompany nerve trauma and influence recovery by affecting blood supply and the integrity of fascicle protection.