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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Veröffentlicht in:PloS one 2016-04, Vol.11 (4), p.e0153835-e0153835
Hauptverfasser: Wang, Liang, Kang, Shuai, Zou, Dingquan, Zhan, Lei, Li, Zhengxi, Zhu, Wan, Su, Hua
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Su, Hua
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 Ccr2RFP/+Cx3cr1GFP/+ 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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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 Ccr2RFP/+Cx3cr1GFP/+ 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. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Liang</au><au>Kang, Shuai</au><au>Zou, Dingquan</au><au>Zhan, Lei</au><au>Li, Zhengxi</au><au>Zhu, Wan</au><au>Su, Hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-04-18</date><risdate>2016</risdate><volume>11</volume><issue>4</issue><spage>e0153835</spage><epage>e0153835</epage><pages>e0153835-e0153835</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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 Ccr2RFP/+Cx3cr1GFP/+ 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27089041</pmid><doi>10.1371/journal.pone.0153835</doi><oa>free_for_read</oa></addata></record>
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subjects Alleles
Analysis
Animal cognition
Animal experimentation
Animals
Apoptosis
Behavior, Animal
Biology and Life Sciences
Bone marrow
Bone surgery
Brain Injuries - etiology
Brain Injuries - metabolism
Brain Injuries - pathology
Brain Ischemia - etiology
Brain Ischemia - metabolism
Brain Ischemia - pathology
Brain research
CCR2 protein
Cerebral blood flow
Cerebral ischemia
Complications and side effects
CX3C Chemokine Receptor 1
CX3CR1 protein
Cytokines - metabolism
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
FDA approval
Fractures (Injuries)
Fractures, Bone - complications
Fractures, Bone - metabolism
Fractures, Bone - pathology
Green fluorescent protein
Health risks
Hospitals
House mouse
Immunoenzyme Techniques
Infarction, Middle Cerebral Artery - physiopathology
Inflammation
Inflammation - etiology
Inflammation - metabolism
Inflammation - pathology
Injuries
Ischemia
Macrophages
Male
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microglia
Microglia - immunology
Microglia - pathology
Monocyte chemoattractant protein 1
Neurons
Neurosurgery
Occlusion
Pain
Proteins
Receptors, CCR2 - physiology
Receptors, Chemokine - physiology
Risk analysis
Risk factors
Risk management
Rodents
Stroke
Stroke - etiology
Stroke - metabolism
Stroke - pathology
Surgery
Tibia
title Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice
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