Editorial
Introduction to special issue: Challenges and opportunities for regeneration in the peripheral nervous system

https://doi.org/10.1016/j.expneurol.2009.12.001Get rights and content

Abstract

Regeneration in the peripheral nervous system offers unique opportunities and challenges to medicine. Compared to the central nervous system, peripheral axons can and do regenerate resulting in functional recovery, especially if the distance to target is short as in distal limb injuries. However, this regenerative capacity is often incomplete and functional recovery with proximal lesions is limited. Furthermore, regeneration of axons to the appropriate targets remains a challenge with inappropriate reinnervation being an impediment to full recovery. The reviews and selected original research papers in this Special Issue will address some of these challenges and highlight new opportunities for development of effective therapies for nerve regeneration.

Introduction

As outlined elsewhere in this introduction and in subsequent reviews, regeneration in the peripheral nervous system (PNS) offers unique challenges and opportunities to clinical and translational neuroscience. This brief overview outlines these challenges and opportunities in two sections focusing on (i) intrinsic and extrinsic determinants of speed and quantity at which nerves can regenerate and (ii) appropriate reinnervation of the correct targets. Clinically relevant functional recovery is dependent on both of these two critical factors.

Section snippets

Increasing the speed and amount of regeneration

Many clinical and pre-clinical animal studies have shown that prompt reinnervation of the end organ is the single most important determinant of good functional recovery. Experience going back to World War II injuries suggests that delay in repairing an injured nerve results in poor functional outcome (Sunderland, 1952, Woodhall and Beebe, 1956). Determinants of such poor recovery after delayed nerve repairs or with proximal injuries are probably multifactorial but include changes in the end

Sustaining regeneration

One of the challenges in translating nerve regeneration studies from small animal models to humans has been the issue of degenerative changes that take place in the denervated segments of the pathway and target tissues. Going back to extensive experience with war injuries during World War II, we know that for a nerve repair to be effective it had to be done in a timely manner as delayed repairs yielded poor functional recoveries (Woodhall and Beebe, 1956). The issue of whether this is an

Promoting reinnervation of functionally appropriate targets

Successful peripheral nerve repair depends not only upon delivery of axons to the periphery but also upon re-establishment of appropriate connections between the periphery and the central nervous system. The consequences of non-specific regeneration are often clinically obvious. Faulty localization of sensory stimuli was first described by John Mitchell in a review of his father's Civil War patients (Mitchell, 1895) and has long been recognized as a hallmark of nerve regeneration. The

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