End-to-side (terminolateral) nerve regeneration: A challenge for neuroscientists coming from an intriguing nerve repair concept

The last 15 years have seen a growing interest regarding a technique for nerve repair named end-to-side (terminolateral) neurorrhaphy. This technique is based on the concept that nerve fiber regeneration along the distal stump of a transected nerve, the proximal stump of which was lost, can be obtained by just suturing the proximal end of its distal stump to the epinerium of a neighbor healthy and undamaged donor nerve. A large body of experimental studies have shown that end-to-side neurorrhaphy, in fact, is able to induce collateral sprouting from donor nerve's axons which is at the basis of the massive repopulation of the distal nerve stump. The regenerating nerve fibers eventually reinnervate the periphery of the severed nerve leading to a recovery of the lost function the degree of which varies depending on factors that still have to be elucidated. Surprisingly, this puzzling concept of nerve regeneration has attracted very little attention from basic neuroscientists so far and, thus, the present paper is intended to call for more biological research on it by overviewing the relevant literature and indicating the several unanswered questions that this concept asks to the neuroscience community.