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Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue
The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase (SFK) activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a de...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316450/ https://www.ncbi.nlm.nih.gov/pubmed/25657738 http://dx.doi.org/10.4103/1673-5374.147949 |
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author | Rosas, Odrick R. Torrado, Aranza I. Santiago, Jose M. Rodriguez, Ana E. Salgado, Iris K. Miranda, Jorge D. |
author_facet | Rosas, Odrick R. Torrado, Aranza I. Santiago, Jose M. Rodriguez, Ana E. Salgado, Iris K. Miranda, Jorge D. |
author_sort | Rosas, Odrick R. |
collection | PubMed |
description | The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase (SFK) activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyramidine (PP2), a selective SFK inhibitor, after spinal cord contusion with the New York University (NYU) impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-injury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin (a guanine nucleotide exchange factor) phosphorylation in the acute phase (4 days post-injury) after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexin1 phosphorylation (activation) by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury. |
format | Online Article Text |
id | pubmed-4316450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-43164502015-02-05 Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue Rosas, Odrick R. Torrado, Aranza I. Santiago, Jose M. Rodriguez, Ana E. Salgado, Iris K. Miranda, Jorge D. Neural Regen Res Research and Report The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase (SFK) activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyramidine (PP2), a selective SFK inhibitor, after spinal cord contusion with the New York University (NYU) impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-injury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin (a guanine nucleotide exchange factor) phosphorylation in the acute phase (4 days post-injury) after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexin1 phosphorylation (activation) by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury. Medknow Publications & Media Pvt Ltd 2014-12-15 /pmc/articles/PMC4316450/ /pubmed/25657738 http://dx.doi.org/10.4103/1673-5374.147949 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research and Report Rosas, Odrick R. Torrado, Aranza I. Santiago, Jose M. Rodriguez, Ana E. Salgado, Iris K. Miranda, Jorge D. Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue |
title | Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue |
title_full | Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue |
title_fullStr | Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue |
title_full_unstemmed | Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue |
title_short | Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue |
title_sort | long-term treatment with pp2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue |
topic | Research and Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316450/ https://www.ncbi.nlm.nih.gov/pubmed/25657738 http://dx.doi.org/10.4103/1673-5374.147949 |
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