EditorialIntroduction to special issue: Challenges and opportunities for regeneration in the peripheral nervous system
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
References (53)
- et al.
Joseph H. Boyes Award. Dispersion of regenerating axons across enclosed neural gaps
J. Hand Surg. [Am]
(1995) - et al.
Specificity of muscle reinnervation after epineurial and individual fascicular suture of the rat sciatic nerve
J. Hand Surg. [Am]
(1983) - et al.
Peripheral nerve reconnection: improvement of long-term functional effects under simulated clinical conditions in the rat
Exp. Neurol.
(1983) - et al.
Peripheral nerve repair in the hand with and without motor sensory differentiation
J. Hand Surg. Am.
(1993) - et al.
Time course of the conditioning lesion effect on axonal regeneration
Brain Res.
(1980) - et al.
Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation
Exp. Neurol.
(2005) - et al.
Quantitative changes in cholinesterase activity of denervated muscle fibers and sole plates
Exp. Neurol.
(1964) - et al.
Differential atrophy of sensory and motor fibers following section of cat peripheral nerves
Brain Res.
(1979) - et al.
Axonal transport of the cytoskeleton in regenerating motor neurons: constancy and change
Brain Res.
(1980) Proteoglycans in axonal regeneration
Exp. Neurol.
(2005)
A decline in glial cell-line-derived neurotrophic factor expression is associated with impaired regeneration after long-term Schwann cell denervation
Exp. Neurol.
Functional results of low median and ulnar nerve repair with intraneural fascicular dissection and electrical fascicular orientation
J. Hand Surg. Am.
Mismatches between peripheral receptor type and central projections after peripheral nerve regeneration
Neurosci. Lett.
A 25-year perspective of peripheral nerve surgery: evolving neuroscientific concepts and clinical significance
J. Hand Surg. Am.
Tubular repair of the median or ulnar nerve in the human forearm: a 5-year follow-up
J. Hand Surg. Br.
Axonal regeneration in the rat sciatic nerve: effect of a conditioning lesion and of dbcAMP
Brain Res.
Spinal axon regeneration induced by elevation of cyclic AMP
Neuron
The transcription factor ATF-3 promotes neurite outgrowth
Mol. Cell Neurosci.
A morphological study of Schwann cells and axonal regeneration in chronically transected human peripheral nerves
J. Hand Surg. [Br]
Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury
Mol. Cell Neurosci.
Cyclic nucleotide content of ciliary and dorsal root ganglia during embryonic development in the chick
Brain Res.
Neural plasticity: Part 3. Responses to lesions in the peripheral nervous system
Phys. Ther.
A reassessment of the accuracy of reinnervation by motoneurons following crushing or freezing of the sciatic or lumbar spinal nerves of rats
Brain
Role of degenerating axon pathways in regeneration of mouse soleus motor axons
J. Physiol.
Preferential motor reinnervation: a sequential double-labeling study
Restorative Neurology and Neuroscience
The mechanical & humoral control of specificity in nerve repair, operative nerve repair and reconstruction
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