Chapter 12: Mechanisms underlying the end-to-side nerve regeneration.

End-to-side (ETS) nerve repair is used in selected clinical cases. The mechanisms, by which regeneration into the attached nerve segment is initiated and occur, are still not fully understood. Based on numerous experimental studies, different mechanisms have been suggested by which regenerating axons are recruited, such as contamination from the proximal nerve segment, collateral sprouting, and terminal regenerating sprouting from the donor nerve. A variety of experimental models, most commonly in the lower and upper extremity of rats, and techniques have been used to shed light on the mechanisms. Retrograde labeling techniques have revealed that collateral sprouting do occur, but is probably, at least as observed in long-term experiments, less important over time. Pruning of branching nerve fibers, induced by the collateral sprouting, is an additional mechanism in this context. Experiments have also focused on the stimuli, including the question of epineurial or perineurial windows, that trigger the sprouting of axons form the donor nerve, which can detected by the use of markers of cellular injury. In the present article, we review studies contributing to clarifications of mechanisms of end-to-side nerve repair, including used experimental techniques. We also stress the importance of the plastic brain.