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  • Review Article
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Advances in peripheral nerve regeneration

Abstract

Rodent models of nerve injury have increased our understanding of peripheral nerve regeneration, but clinical applications have been scarce, partly because such models do not adequately recapitulate the situation in humans. In human injuries, axons are often required to extend over much longer distances than in mice, and injury leaves distal nerve fibres and target tissues without axonal contact for extended amounts of time. Distal Schwann cells undergo atrophy owing to the lack of contact with proximal neurons, which results in reduced expression of neurotrophic growth factors, changes in the extracellular matrix and loss of Schwann cell basal lamina, all of which hamper axonal extension. Furthermore, atrophy and denervation-related changes in target tissues make good functional recovery difficult to achieve even when axons regenerate all the way to the target tissue. To improve functional outcomes in humans, strategies to increase the speed of axonal growth, maintain Schwann cells in a healthy, repair-capable state and keep target tissues receptive to reinnervation are needed. Use of rodent models of chronic denervation will facilitate our understanding of the molecular mechanisms of peripheral nerve regeneration and create the potential to test therapeutic advances.

Key Points

  • Neurons in the PNS are much more capable of regeneration than those in the CNS, yet some peripheral nerve injuries, especially proximal ones, require intervention

  • Rodent models of chronic denervation are better at mimicking human nerve injury than are traditional nerve regeneration models

  • Compared with rodent axons, human axons have a greater distance to travel before reaching the target tissue, so injury leaves the distal nerve stump denervated for a prolonged period

  • During chronic denervation, several cellular changes occur, including neuronal apoptosis, breakdown of Schwann cell tubes, and muscle atrophy; however, the molecular mechanisms underlying these changes are mostly unknown

  • To improve regeneration, research is focusing on increasing the speed of axonal growth, preventing neuronal apoptosis and muscle atrophy, and maintaining a supportive environment in the distal nerve

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Figure 1: Cellular responses to peripheral nerve injury.

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Acknowledgements

The authors' research work is supported by the Dr Miriam and Sheldon Adelson Medical Research Foundation and the Foundation for Peripheral Neuropathy.

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Scheib, J., Höke, A. Advances in peripheral nerve regeneration. Nat Rev Neurol 9, 668–676 (2013). https://doi.org/10.1038/nrneurol.2013.227

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