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Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion
BACKGROUND: Traumatic spinal cord injury (SCI) induces secondary tissue damage that is associated with astrogliosis and inflammation. We previously reported that acute upregulation of a cluster of cell-cycle-related genes contributes to post-mitotic cell death and secondary damage after SCI. However...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410790/ https://www.ncbi.nlm.nih.gov/pubmed/22784881 http://dx.doi.org/10.1186/1742-2094-9-169 |
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author | Wu, Junfang Pajoohesh-Ganji, Ahdeah Stoica, Bogdan A Dinizo, Michael Guanciale, Kelsey Faden, Alan I |
author_facet | Wu, Junfang Pajoohesh-Ganji, Ahdeah Stoica, Bogdan A Dinizo, Michael Guanciale, Kelsey Faden, Alan I |
author_sort | Wu, Junfang |
collection | PubMed |
description | BACKGROUND: Traumatic spinal cord injury (SCI) induces secondary tissue damage that is associated with astrogliosis and inflammation. We previously reported that acute upregulation of a cluster of cell-cycle-related genes contributes to post-mitotic cell death and secondary damage after SCI. However, it remains unclear whether cell cycle activation continues more chronically and contributes to more delayed glial change. Here we examined expression of cell cycle-related proteins up to 4 months following SCI, as well as the effects of the selective cyclin-dependent kinase (CDKs) inhibitor CR8, on astrogliosis and microglial activation in a rat SCI contusion model. METHODS: Adult male rats were subjected to moderate spinal cord contusion injury at T8 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 weeks or 4 months post-injury, and processed for protein expression and lesion volume. Functional recovery was assessed over the 4 months after injury. RESULTS: Immunoblot analysis demonstrated a marked continued upregulation of cell cycle-related proteins − including cyclin D1 and E, CDK4, E2F5 and PCNA − for 4 months post-injury that were highly expressed by GFAP(+) astrocytes and microglia, and co-localized with inflammatory-related proteins. CR8 administrated systemically 3 h post-injury and continued for 7 days limited the sustained elevation of cell cycle proteins and immunoreactivity of GFAP, Iba-1 and p22(PHOX) − a key component of NADPH oxidase − up to 4 months after SCI. CR8 treatment significantly reduced lesion volume, which typically progressed in untreated animals between 1 and 4 months after trauma. Functional recovery was also significantly improved by CR8 treatment after SCI from week 2 through week 16. CONCLUSIONS: These data demonstrate that cell cycle-related proteins are chronically upregulated after SCI and may contribute to astroglial scar formation, chronic inflammation and further tissue loss. |
format | Online Article Text |
id | pubmed-3410790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-34107902012-08-03 Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion Wu, Junfang Pajoohesh-Ganji, Ahdeah Stoica, Bogdan A Dinizo, Michael Guanciale, Kelsey Faden, Alan I J Neuroinflammation Research BACKGROUND: Traumatic spinal cord injury (SCI) induces secondary tissue damage that is associated with astrogliosis and inflammation. We previously reported that acute upregulation of a cluster of cell-cycle-related genes contributes to post-mitotic cell death and secondary damage after SCI. However, it remains unclear whether cell cycle activation continues more chronically and contributes to more delayed glial change. Here we examined expression of cell cycle-related proteins up to 4 months following SCI, as well as the effects of the selective cyclin-dependent kinase (CDKs) inhibitor CR8, on astrogliosis and microglial activation in a rat SCI contusion model. METHODS: Adult male rats were subjected to moderate spinal cord contusion injury at T8 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 weeks or 4 months post-injury, and processed for protein expression and lesion volume. Functional recovery was assessed over the 4 months after injury. RESULTS: Immunoblot analysis demonstrated a marked continued upregulation of cell cycle-related proteins − including cyclin D1 and E, CDK4, E2F5 and PCNA − for 4 months post-injury that were highly expressed by GFAP(+) astrocytes and microglia, and co-localized with inflammatory-related proteins. CR8 administrated systemically 3 h post-injury and continued for 7 days limited the sustained elevation of cell cycle proteins and immunoreactivity of GFAP, Iba-1 and p22(PHOX) − a key component of NADPH oxidase − up to 4 months after SCI. CR8 treatment significantly reduced lesion volume, which typically progressed in untreated animals between 1 and 4 months after trauma. Functional recovery was also significantly improved by CR8 treatment after SCI from week 2 through week 16. CONCLUSIONS: These data demonstrate that cell cycle-related proteins are chronically upregulated after SCI and may contribute to astroglial scar formation, chronic inflammation and further tissue loss. BioMed Central 2012-07-11 /pmc/articles/PMC3410790/ /pubmed/22784881 http://dx.doi.org/10.1186/1742-2094-9-169 Text en Copyright ©2012 Wu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Wu, Junfang Pajoohesh-Ganji, Ahdeah Stoica, Bogdan A Dinizo, Michael Guanciale, Kelsey Faden, Alan I Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion |
title | Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion |
title_full | Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion |
title_fullStr | Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion |
title_full_unstemmed | Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion |
title_short | Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion |
title_sort | delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410790/ https://www.ncbi.nlm.nih.gov/pubmed/22784881 http://dx.doi.org/10.1186/1742-2094-9-169 |
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