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Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest
OBJECTIVES: Acute kidney injury is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (quiescence-inducing neurons-induced h...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9801336/ https://www.ncbi.nlm.nih.gov/pubmed/36590714 http://dx.doi.org/10.1016/j.xjon.2022.11.001 |
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author | Kyo, Shoichi Murata, Kozue Kawatou, Masahide Minatoya, Kenji Sunagawa, Genshiro A. Masumoto, Hidetoshi |
author_facet | Kyo, Shoichi Murata, Kozue Kawatou, Masahide Minatoya, Kenji Sunagawa, Genshiro A. Masumoto, Hidetoshi |
author_sort | Kyo, Shoichi |
collection | PubMed |
description | OBJECTIVES: Acute kidney injury is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (quiescence-inducing neurons-induced hypometabolism [QIH]). Here, we investigated the efficacy of QIH for the amelioration of acute kidney injury in an experimental circulatory arrest using a transgenic mouse model. METHODS: We genetically prepared mice in which QIH can be conditionally induced (QIH-ready mice). Mice were divided into 4 groups (n = 6 for each): QIH-ready normothermia (QN), QIH-ready hypothermia (QH), control normothermia (CN), and control hypothermia (CH). After induction of QIH, left thoracotomy and descending aorta crossclamping were conducted. After reperfusion, we collected kidneys and evaluated histologic changes and serum biochemical markers, specifically neutrophil gelatinase-associated lipocalin and cystatin C, indicating early kidney injury. RESULTS: Normothermia showed higher tubular injury scores than those in hypothermia (QN vs QH [P = .0021] and CN vs CH [P < .001]). QN exhibited lower neutrophil gelatinase-associated lipocalin and cystatin C levels than those in CN (neutrophil gelatinase-associated lipocalin: CN vs QN: 1.51 ± 0.71 vs 0.82 ± 0.32; P = .0414 and cystatin C: 1.48 ± 0.39 vs 0.71 ± 0.26; P = .0015). There was no significant difference between QN and QH. CONCLUSIONS: QIH partly ameliorated acute kidney injury in a mouse ischemia model even in normothermia. QIH might be a promising approach to achieving sufficient kidney protection without hypothermic circulatory arrest in the future. |
format | Online Article Text |
id | pubmed-9801336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-98013362022-12-31 Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest Kyo, Shoichi Murata, Kozue Kawatou, Masahide Minatoya, Kenji Sunagawa, Genshiro A. Masumoto, Hidetoshi JTCVS Open Adult: Coronary: Basic Science OBJECTIVES: Acute kidney injury is a serious complication after cardiovascular surgery requiring circulatory arrest. It is reported that mice can be induced into a hibernation-like hypometabolic state by stimulating a specific neuron located at the hypothalamus (quiescence-inducing neurons-induced hypometabolism [QIH]). Here, we investigated the efficacy of QIH for the amelioration of acute kidney injury in an experimental circulatory arrest using a transgenic mouse model. METHODS: We genetically prepared mice in which QIH can be conditionally induced (QIH-ready mice). Mice were divided into 4 groups (n = 6 for each): QIH-ready normothermia (QN), QIH-ready hypothermia (QH), control normothermia (CN), and control hypothermia (CH). After induction of QIH, left thoracotomy and descending aorta crossclamping were conducted. After reperfusion, we collected kidneys and evaluated histologic changes and serum biochemical markers, specifically neutrophil gelatinase-associated lipocalin and cystatin C, indicating early kidney injury. RESULTS: Normothermia showed higher tubular injury scores than those in hypothermia (QN vs QH [P = .0021] and CN vs CH [P < .001]). QN exhibited lower neutrophil gelatinase-associated lipocalin and cystatin C levels than those in CN (neutrophil gelatinase-associated lipocalin: CN vs QN: 1.51 ± 0.71 vs 0.82 ± 0.32; P = .0414 and cystatin C: 1.48 ± 0.39 vs 0.71 ± 0.26; P = .0015). There was no significant difference between QN and QH. CONCLUSIONS: QIH partly ameliorated acute kidney injury in a mouse ischemia model even in normothermia. QIH might be a promising approach to achieving sufficient kidney protection without hypothermic circulatory arrest in the future. Elsevier 2022-11-08 /pmc/articles/PMC9801336/ /pubmed/36590714 http://dx.doi.org/10.1016/j.xjon.2022.11.001 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Adult: Coronary: Basic Science Kyo, Shoichi Murata, Kozue Kawatou, Masahide Minatoya, Kenji Sunagawa, Genshiro A. Masumoto, Hidetoshi Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest |
title | Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest |
title_full | Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest |
title_fullStr | Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest |
title_full_unstemmed | Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest |
title_short | Quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest |
title_sort | quiescence-inducing neurons-induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest |
topic | Adult: Coronary: Basic Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9801336/ https://www.ncbi.nlm.nih.gov/pubmed/36590714 http://dx.doi.org/10.1016/j.xjon.2022.11.001 |
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