Abstract

Mammalian peripheral nerve fibres can regenerate after injury. Repair is most likely to succeed if axons are simply crushed or have only a very short (less than 0.5 cm) interstump gap to cross and most likely to fail if the interstump gap is long (greater than 1 cm) and associated with soft tissue damage. Whereas reactive axonal sprouting appears to be an intrinsic neuronal response to injury, the subsequent organization of the axonal sprouts, in particular their orderly outgrowth in minifascicles towards a distant distal stump does not occur unless Schwann cells are present. During the injury response, Schwann cells proliferate; co-migrate with regrowing axons (when the proximal stump is separated from the distal stump); respond to axonal cues by transient upregulation or re-expression of molecules which provide a favourable substrate for axonal extension; and attract bundles of regrowing axons and their associated Schwann cells across interstump gaps up to 1 cm in length. Recruited macrophages remove myelin debris from the Schwann cell tubes; they probably interact with Schwann cells in other ways during the injury response, e.g. by presenting mitogens and cytokines.

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