Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice

Chi Him Eddie Ma, Takao Omura, Enrique J. Cobos, Alban Latrémolière, Nader Ghasemlou, Gary J. Brenner, Ed Van Veen, Lee Barrett, Tomokazu Sawada, Fuying Gao, Giovanni Coppola, Frank Gertler, Michael Costigan, Dan Geschwind, Clifford J. Woolf

Research output: Contribution to journalArticle

Abstract

Although peripheral nerves can regenerate after injury, proximal nerve injury in humans results in minimal restoration of motor function. One possible explanation for this is that injury-induced axonal growth is too slow. Heat shock protein 27 (Hsp27) is a regeneration-associated protein that accelerates axonal growth in vitro. Here, we have shown that it can also do this in mice after peripheral nerve injury. While rapid motor and sensory recovery occurred in mice after a sciatic nerve crush injury, there was little return of motor function after sciatic nerve transection, because of the delay in motor axons reaching their target. This was not due to a failure of axonal growth, because injured motor axons eventually fully re-extended into muscles and sensory function returned; rather, it resulted from a lack of motor end plate reinnervation. Tg mice expressing high levels of Hsp27 demonstrated enhanced restoration of motor function after nerve transection/resuture by enabling motor synapse reinnervation, but only within 5 weeks of injury. In humans with peripheral nerve injuries, shorter wait times to decompression surgery led to improved functional recovery, and, while a return of sensation occurred in all patients, motor recovery was limited. Thus, absence of motor recovery after nerve damage may result from a failure of synapse reformation after prolonged denervation rather than a failure of axonal growth.

Original languageEnglish (US)
Pages (from-to)4332-4347
Number of pages16
JournalJournal of Clinical Investigation
Volume121
Issue number11
DOIs
StatePublished - Nov 1 2011

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ma, C. H. E., Omura, T., Cobos, E. J., Latrémolière, A., Ghasemlou, N., Brenner, G. J., Van Veen, E., Barrett, L., Sawada, T., Gao, F., Coppola, G., Gertler, F., Costigan, M., Geschwind, D., & Woolf, C. J. (2011). Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice. Journal of Clinical Investigation, 121(11), 4332-4347. https://doi.org/10.1172/JCI58675