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Complement C6 deficiency exacerbates pathophysiology after spinal cord injury

Historically, the membrane attack complex, composed of complement components C5b-9, has been connected to lytic cell death and implicated in secondary injury after a CNS insult. However, studies to date have utilized either non-littermate control rat models, or mouse models that lack significant C5b...

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Autores principales: Su, Diane, Hooshmand, Mitra J., Galvan, Manuel D., Nishi, Rebecca A., Cummings, Brian J., Anderson, Aileen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659012/
https://www.ncbi.nlm.nih.gov/pubmed/33177623
http://dx.doi.org/10.1038/s41598-020-76441-3
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author Su, Diane
Hooshmand, Mitra J.
Galvan, Manuel D.
Nishi, Rebecca A.
Cummings, Brian J.
Anderson, Aileen J.
author_facet Su, Diane
Hooshmand, Mitra J.
Galvan, Manuel D.
Nishi, Rebecca A.
Cummings, Brian J.
Anderson, Aileen J.
author_sort Su, Diane
collection PubMed
description Historically, the membrane attack complex, composed of complement components C5b-9, has been connected to lytic cell death and implicated in secondary injury after a CNS insult. However, studies to date have utilized either non-littermate control rat models, or mouse models that lack significant C5b-9 activity. To investigate what role C5b-9 plays in spinal cord injury and recovery, we generated littermate PVG C6 wildtype and deficient rats and tested functional and histological recovery after moderate contusion injury using the Infinite Horizon Impactor. We compare the effect of C6 deficiency on recovery of locomotor function and histological injury parameters in PVG rats under two conditions: (1) animals maintained as separate C6 WT and C6-D homozygous colonies; and (2) establishment of a heterozygous colony to generate C6 WT and C6-D littermate controls. The results suggest that maintenance of separate homozygous colonies is inadequate for testing the effect of C6 deficiency on locomotor and histological recovery after SCI, and highlight the importance of using littermate controls in studies involving genetic manipulation of the complement cascade.
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spelling pubmed-76590122020-11-13 Complement C6 deficiency exacerbates pathophysiology after spinal cord injury Su, Diane Hooshmand, Mitra J. Galvan, Manuel D. Nishi, Rebecca A. Cummings, Brian J. Anderson, Aileen J. Sci Rep Article Historically, the membrane attack complex, composed of complement components C5b-9, has been connected to lytic cell death and implicated in secondary injury after a CNS insult. However, studies to date have utilized either non-littermate control rat models, or mouse models that lack significant C5b-9 activity. To investigate what role C5b-9 plays in spinal cord injury and recovery, we generated littermate PVG C6 wildtype and deficient rats and tested functional and histological recovery after moderate contusion injury using the Infinite Horizon Impactor. We compare the effect of C6 deficiency on recovery of locomotor function and histological injury parameters in PVG rats under two conditions: (1) animals maintained as separate C6 WT and C6-D homozygous colonies; and (2) establishment of a heterozygous colony to generate C6 WT and C6-D littermate controls. The results suggest that maintenance of separate homozygous colonies is inadequate for testing the effect of C6 deficiency on locomotor and histological recovery after SCI, and highlight the importance of using littermate controls in studies involving genetic manipulation of the complement cascade. Nature Publishing Group UK 2020-11-11 /pmc/articles/PMC7659012/ /pubmed/33177623 http://dx.doi.org/10.1038/s41598-020-76441-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Su, Diane
Hooshmand, Mitra J.
Galvan, Manuel D.
Nishi, Rebecca A.
Cummings, Brian J.
Anderson, Aileen J.
Complement C6 deficiency exacerbates pathophysiology after spinal cord injury
title Complement C6 deficiency exacerbates pathophysiology after spinal cord injury
title_full Complement C6 deficiency exacerbates pathophysiology after spinal cord injury
title_fullStr Complement C6 deficiency exacerbates pathophysiology after spinal cord injury
title_full_unstemmed Complement C6 deficiency exacerbates pathophysiology after spinal cord injury
title_short Complement C6 deficiency exacerbates pathophysiology after spinal cord injury
title_sort complement c6 deficiency exacerbates pathophysiology after spinal cord injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659012/
https://www.ncbi.nlm.nih.gov/pubmed/33177623
http://dx.doi.org/10.1038/s41598-020-76441-3
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