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Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice

Ischemic stroke is a devastating complication of bone fracture. Bone fracture shortly after stroke enhances stroke injury by augmenting inflammation. We hypothesize that bone fracture shortly before ischemic stroke also exacerbates ischemic cerebral injury. Tibia fracture was performed 6 or 24 hours...

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Autores principales: Wang, Liang, Kang, Shuai, Zou, Dingquan, Zhan, Lei, Li, Zhengxi, Zhu, Wan, Su, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835054/
https://www.ncbi.nlm.nih.gov/pubmed/27089041
http://dx.doi.org/10.1371/journal.pone.0153835
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author Wang, Liang
Kang, Shuai
Zou, Dingquan
Zhan, Lei
Li, Zhengxi
Zhu, Wan
Su, Hua
author_facet Wang, Liang
Kang, Shuai
Zou, Dingquan
Zhan, Lei
Li, Zhengxi
Zhu, Wan
Su, Hua
author_sort Wang, Liang
collection PubMed
description Ischemic stroke is a devastating complication of bone fracture. Bone fracture shortly after stroke enhances stroke injury by augmenting inflammation. We hypothesize that bone fracture shortly before ischemic stroke also exacerbates ischemic cerebral injury. Tibia fracture was performed 6 or 24 hours before permanent middle cerebral artery occlusion (pMCAO) on C57BL/6J mice or Ccr2(RFP/+)Cx3cr1(GFP/+) mice that have the RFP gene knocked into one allele of Ccr2 gene and GFP gene knocked into one allele of Cx3cr1 gene. Behavior was tested 3 days after pMCAO. Infarct volume, the number of CD68(+) cells, apoptotic neurons, bone marrow-derived macrophages (RFP(+)), and microgila (GFP(+)) in the peri-infarct region were quantified. Compared to mice subjected to pMCAO only, bone fracture 6 or 24 hours before pMCAO increased behavioral deficits, the infarct volume, and the number of CD68(+) cells and apoptotic neurons in the peri-infarct area. Both bone marrow-derived macrophages (CCR2(+)) and microglia (CX3CR1(+)) increased in the peri-infarct regions of mice subjected to bone fracture before pMCAO compared to stroke-only mice. The mice subjected to bone fracture 6 hours before pMCAO had more severe injury than mice that had bone fracture 24 hours before pMCAO. Our data showed that bone fracture shortly before stroke also increases neuroinflammation and exacerbates ischemic cerebral injury. Our findings suggest that inhibition of neuroinflammation or management of stroke risk factors before major bone surgery would be beneficial for patients who are likely to suffer from stroke.
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spelling pubmed-48350542016-04-29 Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice Wang, Liang Kang, Shuai Zou, Dingquan Zhan, Lei Li, Zhengxi Zhu, Wan Su, Hua PLoS One Research Article Ischemic stroke is a devastating complication of bone fracture. Bone fracture shortly after stroke enhances stroke injury by augmenting inflammation. We hypothesize that bone fracture shortly before ischemic stroke also exacerbates ischemic cerebral injury. Tibia fracture was performed 6 or 24 hours before permanent middle cerebral artery occlusion (pMCAO) on C57BL/6J mice or Ccr2(RFP/+)Cx3cr1(GFP/+) mice that have the RFP gene knocked into one allele of Ccr2 gene and GFP gene knocked into one allele of Cx3cr1 gene. Behavior was tested 3 days after pMCAO. Infarct volume, the number of CD68(+) cells, apoptotic neurons, bone marrow-derived macrophages (RFP(+)), and microgila (GFP(+)) in the peri-infarct region were quantified. Compared to mice subjected to pMCAO only, bone fracture 6 or 24 hours before pMCAO increased behavioral deficits, the infarct volume, and the number of CD68(+) cells and apoptotic neurons in the peri-infarct area. Both bone marrow-derived macrophages (CCR2(+)) and microglia (CX3CR1(+)) increased in the peri-infarct regions of mice subjected to bone fracture before pMCAO compared to stroke-only mice. The mice subjected to bone fracture 6 hours before pMCAO had more severe injury than mice that had bone fracture 24 hours before pMCAO. Our data showed that bone fracture shortly before stroke also increases neuroinflammation and exacerbates ischemic cerebral injury. Our findings suggest that inhibition of neuroinflammation or management of stroke risk factors before major bone surgery would be beneficial for patients who are likely to suffer from stroke. Public Library of Science 2016-04-18 /pmc/articles/PMC4835054/ /pubmed/27089041 http://dx.doi.org/10.1371/journal.pone.0153835 Text en © 2016 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wang, Liang
Kang, Shuai
Zou, Dingquan
Zhan, Lei
Li, Zhengxi
Zhu, Wan
Su, Hua
Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice
title Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice
title_full Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice
title_fullStr Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice
title_full_unstemmed Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice
title_short Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice
title_sort bone fracture pre-ischemic stroke exacerbates ischemic cerebral injury in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835054/
https://www.ncbi.nlm.nih.gov/pubmed/27089041
http://dx.doi.org/10.1371/journal.pone.0153835
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