Endoneurium

Endoneurium is the innermost connective tissue layer surrounding individual nerve fibers within peripheral nerves. It envelopes each axon and its Schwann cell sheath, lying inside the perineurium and epineurium. The endoneurial space is bounded by a basal lamina around each fiber and contains a delicate matrix of loose connective tissue, predominantly type III collagen, reticular fibers, fibroblasts, and an extensive capillary network. Resident macrophages and occasional mast cells may also be present.

The endoneurium provides physical support and a specialized microenvironment for axons and Schwann cells. Its capillaries contribute to the supply of nutrients and removal of metabolites, and together with the endothelial barriers help maintain the endoneurial fluid environment. The endoneurial tubes formed around regenerated axons guide nerve fiber regrowth after injury.

In clinical terms, the endoneurium can be involved in various peripheral nerve conditions. Trauma, inflammation, or fibrotic scarring can disrupt the endoneurial tubes and impede regeneration, whereas intact endoneurial architecture supports more accurate reinnervation.

It is distinct from the perineurium, which encloses nerve fascicles, and the epineurium, which surrounds the entire nerve.