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

Wang L, Kang S, Zou D, Zhan L, Li Z, Zhu W, Su H - PLoS ONE (2016)

Bottom Line: Behavior was tested 3 days after 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California San Francisco, San Francisco, California, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

Bone fracture increased both microglia and bone marrow-derived macrophages in the peri-infarct region.(A-C) Representative image of Cx3cr1 positive cells (green, A), Ccr2 positive cells (red, B), and Cx3cr1 and Ccr2, double positive cells (yellow, C). (D) Quantification of Cx3cr1+, Ccr2+ and Ccr2 and Cx3cr1 double positive cells in the peri-infarct region. *: P = 0.001, compared to stroke-only group, #: P = 0.001, compared to mice that received tibia fracture 24-hours before pMCAO. $: P<0.001 compared to stroke-only group, &: P = 0.01 compared to bone fracture 24 hours before pMCAO group. ^: P<0.001 compared to bone fracture 24-hours before pMCAO group. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h stroke: tibia fracture 24 hours before pMCAO. Scale bar: 50μm.
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pone.0153835.g006: Bone fracture increased both microglia and bone marrow-derived macrophages in the peri-infarct region.(A-C) Representative image of Cx3cr1 positive cells (green, A), Ccr2 positive cells (red, B), and Cx3cr1 and Ccr2, double positive cells (yellow, C). (D) Quantification of Cx3cr1+, Ccr2+ and Ccr2 and Cx3cr1 double positive cells in the peri-infarct region. *: P = 0.001, compared to stroke-only group, #: P = 0.001, compared to mice that received tibia fracture 24-hours before pMCAO. $: P<0.001 compared to stroke-only group, &: P = 0.01 compared to bone fracture 24 hours before pMCAO group. ^: P<0.001 compared to bone fracture 24-hours before pMCAO group. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h stroke: tibia fracture 24 hours before pMCAO. Scale bar: 50μm.

Mentions: Mice that had bone fracture 6-hours before pMCAO also had more bone marrow-derived macrophages (40.4±9.78% of DAPI labeled nuclei, CCR2+) in the peri-infarct regions compared to stroke-only mice (24.4±5.15%, p = 0.001) and bone fracture 24 hours before pMCAO mice (24.0±5.57%, p = 0.001, Fig 6B & 6D). Mice that received bone fracture 6 hours before pMCAO also had more microglia (39.6±3.66%, CX3CR1+) in the peri-infarct regions compared to stroke-only mice (24.2±4.88%, p <0.001, Fig 6A & 6D) and mice that received bone fracture 24 hours before pMCAO (31.4±5.54%, p = 0.01, Fig 6D).


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

Wang L, Kang S, Zou D, Zhan L, Li Z, Zhu W, Su H - PLoS ONE (2016)

Bone fracture increased both microglia and bone marrow-derived macrophages in the peri-infarct region.(A-C) Representative image of Cx3cr1 positive cells (green, A), Ccr2 positive cells (red, B), and Cx3cr1 and Ccr2, double positive cells (yellow, C). (D) Quantification of Cx3cr1+, Ccr2+ and Ccr2 and Cx3cr1 double positive cells in the peri-infarct region. *: P = 0.001, compared to stroke-only group, #: P = 0.001, compared to mice that received tibia fracture 24-hours before pMCAO. $: P<0.001 compared to stroke-only group, &: P = 0.01 compared to bone fracture 24 hours before pMCAO group. ^: P<0.001 compared to bone fracture 24-hours before pMCAO group. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h stroke: tibia fracture 24 hours before pMCAO. Scale bar: 50μm.
© Copyright Policy
Related In: Results  -  Collection

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pone.0153835.g006: Bone fracture increased both microglia and bone marrow-derived macrophages in the peri-infarct region.(A-C) Representative image of Cx3cr1 positive cells (green, A), Ccr2 positive cells (red, B), and Cx3cr1 and Ccr2, double positive cells (yellow, C). (D) Quantification of Cx3cr1+, Ccr2+ and Ccr2 and Cx3cr1 double positive cells in the peri-infarct region. *: P = 0.001, compared to stroke-only group, #: P = 0.001, compared to mice that received tibia fracture 24-hours before pMCAO. $: P<0.001 compared to stroke-only group, &: P = 0.01 compared to bone fracture 24 hours before pMCAO group. ^: P<0.001 compared to bone fracture 24-hours before pMCAO group. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h stroke: tibia fracture 24 hours before pMCAO. Scale bar: 50μm.
Mentions: Mice that had bone fracture 6-hours before pMCAO also had more bone marrow-derived macrophages (40.4±9.78% of DAPI labeled nuclei, CCR2+) in the peri-infarct regions compared to stroke-only mice (24.4±5.15%, p = 0.001) and bone fracture 24 hours before pMCAO mice (24.0±5.57%, p = 0.001, Fig 6B & 6D). Mice that received bone fracture 6 hours before pMCAO also had more microglia (39.6±3.66%, CX3CR1+) in the peri-infarct regions compared to stroke-only mice (24.2±4.88%, p <0.001, Fig 6A & 6D) and mice that received bone fracture 24 hours before pMCAO (31.4±5.54%, p = 0.01, Fig 6D).

Bottom Line: Behavior was tested 3 days after 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California San Francisco, San Francisco, California, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus