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Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation

Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory sign...

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Autores principales: Nagai, Jun, Kitamura, Yoshiteru, Owada, Kazuki, Yamashita, Naoya, Takei, Kohtaro, Goshima, Yoshio, Ohshima, Toshio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317684/
https://www.ncbi.nlm.nih.gov/pubmed/25652774
http://dx.doi.org/10.1038/srep08269
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author Nagai, Jun
Kitamura, Yoshiteru
Owada, Kazuki
Yamashita, Naoya
Takei, Kohtaro
Goshima, Yoshio
Ohshima, Toshio
author_facet Nagai, Jun
Kitamura, Yoshiteru
Owada, Kazuki
Yamashita, Naoya
Takei, Kohtaro
Goshima, Yoshio
Ohshima, Toshio
author_sort Nagai, Jun
collection PubMed
description Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4−/− mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI.
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spelling pubmed-43176842015-02-11 Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation Nagai, Jun Kitamura, Yoshiteru Owada, Kazuki Yamashita, Naoya Takei, Kohtaro Goshima, Yoshio Ohshima, Toshio Sci Rep Article Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4−/− mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI. Nature Publishing Group 2015-02-05 /pmc/articles/PMC4317684/ /pubmed/25652774 http://dx.doi.org/10.1038/srep08269 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Nagai, Jun
Kitamura, Yoshiteru
Owada, Kazuki
Yamashita, Naoya
Takei, Kohtaro
Goshima, Yoshio
Ohshima, Toshio
Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation
title Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation
title_full Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation
title_fullStr Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation
title_full_unstemmed Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation
title_short Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation
title_sort crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317684/
https://www.ncbi.nlm.nih.gov/pubmed/25652774
http://dx.doi.org/10.1038/srep08269
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