Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1782355714295988224 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4317684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT nagaijun crmp4deletionpromotesrecoveryfromspinalcordinjurybyneuroprotectionandlimitedscarformation AT kitamurayoshiteru crmp4deletionpromotesrecoveryfromspinalcordinjurybyneuroprotectionandlimitedscarformation AT owadakazuki crmp4deletionpromotesrecoveryfromspinalcordinjurybyneuroprotectionandlimitedscarformation AT yamashitanaoya crmp4deletionpromotesrecoveryfromspinalcordinjurybyneuroprotectionandlimitedscarformation AT takeikohtaro crmp4deletionpromotesrecoveryfromspinalcordinjurybyneuroprotectionandlimitedscarformation AT goshimayoshio crmp4deletionpromotesrecoveryfromspinalcordinjurybyneuroprotectionandlimitedscarformation AT ohshimatoshio crmp4deletionpromotesrecoveryfromspinalcordinjurybyneuroprotectionandlimitedscarformation |