Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice
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 accele...
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| Format: | Article |
| Language: | en_US |
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American Society for Clinical Investigation
2012
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| Online Access: | http://hdl.handle.net/1721.1/73615 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1826191121867341824 |
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| author | Gertler, Frank Ma, Chi Him Eddie Omura, Takao Cobos, Enrique J. Latrémolière, Alban Ghasemlou, Nader Brenner, Gary J. Barrett, Lee Sawada, Tomokazu Gao, Fuying Coppola, Giovanni Costigan, Michael Geschwind, Dan Woolf, Clifford J. Van Veen, John |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Gertler, Frank Ma, Chi Him Eddie Omura, Takao Cobos, Enrique J. Latrémolière, Alban Ghasemlou, Nader Brenner, Gary J. Barrett, Lee Sawada, Tomokazu Gao, Fuying Coppola, Giovanni Costigan, Michael Geschwind, Dan Woolf, Clifford J. Van Veen, John |
| author_sort | Gertler, Frank |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:50:34Z |
| format | Article |
| id | mit-1721.1/73615 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:50:34Z |
| publishDate | 2012 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | mit-1721.1/736152022-09-30T11:38:20Z Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice Gertler, Frank Ma, Chi Him Eddie Omura, Takao Cobos, Enrique J. Latrémolière, Alban Ghasemlou, Nader Brenner, Gary J. Barrett, Lee Sawada, Tomokazu Gao, Fuying Coppola, Giovanni Costigan, Michael Geschwind, Dan Woolf, Clifford J. Van Veen, John Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Gertler, Frank Veen, Ed van 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. 2012-10-04T18:47:57Z 2012-10-04T18:47:57Z 2011-10 2011-08 Article http://purl.org/eprint/type/JournalArticle 0021-9738 1558-8238 http://hdl.handle.net/1721.1/73615 Ma, Chi Him Eddie et al. “Accelerating Axonal Growth Promotes Motor Recovery After Peripheral Nerve Injury in Mice.” Journal of Clinical Investigation 121.11 (2011): 4332–4347. © 2011 American Society for Clinical Investigation https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1172/jci58675 Journal of Clinical Investigation Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Society for Clinical Investigation American Society for Clinical Investigation |
| spellingShingle | Gertler, Frank Ma, Chi Him Eddie Omura, Takao Cobos, Enrique J. Latrémolière, Alban Ghasemlou, Nader Brenner, Gary J. Barrett, Lee Sawada, Tomokazu Gao, Fuying Coppola, Giovanni Costigan, Michael Geschwind, Dan Woolf, Clifford J. Van Veen, John Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice |
| title | Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice |
| title_full | Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice |
| title_fullStr | Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice |
| title_full_unstemmed | Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice |
| title_short | Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice |
| title_sort | accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice |
| url | http://hdl.handle.net/1721.1/73615 https://orcid.org/0000-0003-3214-4554 |
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