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Deficiency of complement receptors CR2/CR1 in Cr2(-/-) mice reduces the extent of secondary brain damage after closed head injury
Complement activation at the C3 convertase level has been associated with acute neuroinflammation and secondary brain injury after severe head trauma. The present study was designed to test the hypothesis that Cr2( -/- ) mice, which lack the receptors CR2/CD21 and CR1/CD35 for complement C3-derived...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050415/ https://www.ncbi.nlm.nih.gov/pubmed/24885042 http://dx.doi.org/10.1186/1742-2094-11-95 |
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author | Neher, Miriam D Rich, Megan C Keene, Chesleigh N Weckbach, Sebastian Bolden, Ashley L Losacco, Justin T Patane, Jenée Flierl, Michael A Kulik, Liudmila Holers, V Michael Stahel, Philip F |
author_facet | Neher, Miriam D Rich, Megan C Keene, Chesleigh N Weckbach, Sebastian Bolden, Ashley L Losacco, Justin T Patane, Jenée Flierl, Michael A Kulik, Liudmila Holers, V Michael Stahel, Philip F |
author_sort | Neher, Miriam D |
collection | PubMed |
description | Complement activation at the C3 convertase level has been associated with acute neuroinflammation and secondary brain injury after severe head trauma. The present study was designed to test the hypothesis that Cr2( -/- ) mice, which lack the receptors CR2/CD21 and CR1/CD35 for complement C3-derived activation fragments, are protected from adverse sequelae of experimental closed head injury. Adult wild-type mice and Cr2( -/- ) mice on a C57BL/6 genetic background were subjected to focal closed head injury using a standardized weight-drop device. Head-injured Cr2( -/- ) mice showed significantly improved neurological outcomes for up to 72 hours after trauma and a significantly decreased post-injury mortality when compared to wild-type mice. In addition, the Cr2( -/- ) genotype was associated with a decreased extent of neuronal cell death at seven days post-injury. Western blot analysis revealed that complement C3 levels were reduced in the injured brain hemispheres of Cr2( -/- ) mice, whereas plasma C3 levels remained unchanged, compared to wild-type mice. Finally, head-injured Cr2( -/- ) had an attenuated extent of post-injury C3 tissue deposition, decreased astrocytosis and microglial activation, and attenuated immunoglobulin M deposition in injured brains compared to wild-type mice. Targeting of these receptors for complement C3 fragments (CR2/CR1) may represent a promising future approach for therapeutic immunomodulation after traumatic brain injury. |
format | Online Article Text |
id | pubmed-4050415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40504152014-06-11 Deficiency of complement receptors CR2/CR1 in Cr2(-/-) mice reduces the extent of secondary brain damage after closed head injury Neher, Miriam D Rich, Megan C Keene, Chesleigh N Weckbach, Sebastian Bolden, Ashley L Losacco, Justin T Patane, Jenée Flierl, Michael A Kulik, Liudmila Holers, V Michael Stahel, Philip F J Neuroinflammation Research Complement activation at the C3 convertase level has been associated with acute neuroinflammation and secondary brain injury after severe head trauma. The present study was designed to test the hypothesis that Cr2( -/- ) mice, which lack the receptors CR2/CD21 and CR1/CD35 for complement C3-derived activation fragments, are protected from adverse sequelae of experimental closed head injury. Adult wild-type mice and Cr2( -/- ) mice on a C57BL/6 genetic background were subjected to focal closed head injury using a standardized weight-drop device. Head-injured Cr2( -/- ) mice showed significantly improved neurological outcomes for up to 72 hours after trauma and a significantly decreased post-injury mortality when compared to wild-type mice. In addition, the Cr2( -/- ) genotype was associated with a decreased extent of neuronal cell death at seven days post-injury. Western blot analysis revealed that complement C3 levels were reduced in the injured brain hemispheres of Cr2( -/- ) mice, whereas plasma C3 levels remained unchanged, compared to wild-type mice. Finally, head-injured Cr2( -/- ) had an attenuated extent of post-injury C3 tissue deposition, decreased astrocytosis and microglial activation, and attenuated immunoglobulin M deposition in injured brains compared to wild-type mice. Targeting of these receptors for complement C3 fragments (CR2/CR1) may represent a promising future approach for therapeutic immunomodulation after traumatic brain injury. BioMed Central 2014-05-24 /pmc/articles/PMC4050415/ /pubmed/24885042 http://dx.doi.org/10.1186/1742-2094-11-95 Text en Copyright © 2014 Neher 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 credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Neher, Miriam D Rich, Megan C Keene, Chesleigh N Weckbach, Sebastian Bolden, Ashley L Losacco, Justin T Patane, Jenée Flierl, Michael A Kulik, Liudmila Holers, V Michael Stahel, Philip F Deficiency of complement receptors CR2/CR1 in Cr2(-/-) mice reduces the extent of secondary brain damage after closed head injury |
title | Deficiency of complement receptors CR2/CR1 in Cr2(-/-) mice reduces the extent of secondary brain damage after closed head injury |
title_full | Deficiency of complement receptors CR2/CR1 in Cr2(-/-) mice reduces the extent of secondary brain damage after closed head injury |
title_fullStr | Deficiency of complement receptors CR2/CR1 in Cr2(-/-) mice reduces the extent of secondary brain damage after closed head injury |
title_full_unstemmed | Deficiency of complement receptors CR2/CR1 in Cr2(-/-) mice reduces the extent of secondary brain damage after closed head injury |
title_short | Deficiency of complement receptors CR2/CR1 in Cr2(-/-) mice reduces the extent of secondary brain damage after closed head injury |
title_sort | deficiency of complement receptors cr2/cr1 in cr2(-/-) mice reduces the extent of secondary brain damage after closed head injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050415/ https://www.ncbi.nlm.nih.gov/pubmed/24885042 http://dx.doi.org/10.1186/1742-2094-11-95 |
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