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A porcine model to study the effect of brain death on kidney genomic responses

INTRODUCTION: A majority of transplanted organs come from donors after brain death (BD). Renal grafts from these donors have higher delayed graft function and lower long-term survival rates compared to living donors. We designed a novel porcine BD model to better delineate the incompletely understoo...

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Autores principales: Sally, Mitchell B., Malinoski, Darren J., Zaldivar, Frank P., Le, Tony, Khoshnevis, Matin, Pinette, William A., Hutchens, Michael, Radom-Aizik, Shlomit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374499/
https://www.ncbi.nlm.nih.gov/pubmed/30800478
http://dx.doi.org/10.1017/cts.2018.312
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author Sally, Mitchell B.
Malinoski, Darren J.
Zaldivar, Frank P.
Le, Tony
Khoshnevis, Matin
Pinette, William A.
Hutchens, Michael
Radom-Aizik, Shlomit
author_facet Sally, Mitchell B.
Malinoski, Darren J.
Zaldivar, Frank P.
Le, Tony
Khoshnevis, Matin
Pinette, William A.
Hutchens, Michael
Radom-Aizik, Shlomit
author_sort Sally, Mitchell B.
collection PubMed
description INTRODUCTION: A majority of transplanted organs come from donors after brain death (BD). Renal grafts from these donors have higher delayed graft function and lower long-term survival rates compared to living donors. We designed a novel porcine BD model to better delineate the incompletely understood inflammatory response to BD, hypothesizing that adhesion molecule pathways would be upregulated in BD. METHODS: Animals were anesthetized and instrumented with monitors and a balloon catheter, then randomized to control and BD groups. BD was induced by inflating the balloon catheter and animals were maintained for 6 hours. RNA was extracted from kidneys, and gene expression pattern was determined. RESULTS: In total, 902 gene pairs were differently expressed between groups. Eleven selected pathways were upregulated after BD, including cell adhesion molecules. CONCLUSIONS: These results should be confirmed in human organ donors. Treatment strategies should target involved pathways and lessen the negative effects of BD on transplantable organs.
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spelling pubmed-63744992019-02-20 A porcine model to study the effect of brain death on kidney genomic responses Sally, Mitchell B. Malinoski, Darren J. Zaldivar, Frank P. Le, Tony Khoshnevis, Matin Pinette, William A. Hutchens, Michael Radom-Aizik, Shlomit J Clin Transl Sci Basic and Preclinical Research INTRODUCTION: A majority of transplanted organs come from donors after brain death (BD). Renal grafts from these donors have higher delayed graft function and lower long-term survival rates compared to living donors. We designed a novel porcine BD model to better delineate the incompletely understood inflammatory response to BD, hypothesizing that adhesion molecule pathways would be upregulated in BD. METHODS: Animals were anesthetized and instrumented with monitors and a balloon catheter, then randomized to control and BD groups. BD was induced by inflating the balloon catheter and animals were maintained for 6 hours. RNA was extracted from kidneys, and gene expression pattern was determined. RESULTS: In total, 902 gene pairs were differently expressed between groups. Eleven selected pathways were upregulated after BD, including cell adhesion molecules. CONCLUSIONS: These results should be confirmed in human organ donors. Treatment strategies should target involved pathways and lessen the negative effects of BD on transplantable organs. Cambridge University Press 2018-10-30 /pmc/articles/PMC6374499/ /pubmed/30800478 http://dx.doi.org/10.1017/cts.2018.312 Text en © The Association for Clinical and Translational Science 2018 http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article, distributed under the terms of the Creative Commons Attribution- NonCommercial-NoDerivatives licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
spellingShingle Basic and Preclinical Research
Sally, Mitchell B.
Malinoski, Darren J.
Zaldivar, Frank P.
Le, Tony
Khoshnevis, Matin
Pinette, William A.
Hutchens, Michael
Radom-Aizik, Shlomit
A porcine model to study the effect of brain death on kidney genomic responses
title A porcine model to study the effect of brain death on kidney genomic responses
title_full A porcine model to study the effect of brain death on kidney genomic responses
title_fullStr A porcine model to study the effect of brain death on kidney genomic responses
title_full_unstemmed A porcine model to study the effect of brain death on kidney genomic responses
title_short A porcine model to study the effect of brain death on kidney genomic responses
title_sort porcine model to study the effect of brain death on kidney genomic responses
topic Basic and Preclinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374499/
https://www.ncbi.nlm.nih.gov/pubmed/30800478
http://dx.doi.org/10.1017/cts.2018.312
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