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

TitleAccelerating axonal growth promotes motor recovery after peripheral nerve injury in mice.
Publication TypeJournal Article
Year of Publication2011
AuthorsMa, CHE, Omura T, Cobos EJ, Latrémolière A, Ghasemlou N, Brenner GJ, van Veen E, Barrett L, Sawada T, Gao F, Coppola G, Gertler F, Costigan M, Geschwind D, Woolf CJ
JournalThe Journal of clinical investigation
Volume121
Issue11
Pagination4332-47
Date Published2011 Nov
ISSN1558-8238
KeywordsAnimals, Axons, Disease Models, Animal, Gene Expression, HSP27 Heat-Shock Proteins, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Motor Endplate, Nerve Regeneration, Peripheral Nerve Injuries, Recovery of Function, Sciatic Nerve, Time Factors
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.

DOI10.1111/j.1460-9568.2012.08054.x
Alternate JournalJ. Clin. Invest.