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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 CD68+ macrophages in the peri-infarct region.(A) Image illustrates infarct core (Core), infarct border (dotted line) and the peri-infarct region (P.I.). (B) Quantification of CD68+ cells. *: P = 0.004, compared to stroke-only group. (C) Representative images of anti-CD68 antibody-stained sections. BF + 6hS: mice that received tibia fracture 6 hours before pMCAO; BF+1dS: mice that received tibia fracture 24 hours before pMCAO. Scale bars: 50μm. N = 6.
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pone.0153835.g005: Bone fracture increased CD68+ macrophages in the peri-infarct region.(A) Image illustrates infarct core (Core), infarct border (dotted line) and the peri-infarct region (P.I.). (B) Quantification of CD68+ cells. *: P = 0.004, compared to stroke-only group. (C) Representative images of anti-CD68 antibody-stained sections. BF + 6hS: mice that received tibia fracture 6 hours before pMCAO; BF+1dS: mice that received tibia fracture 24 hours before pMCAO. Scale bars: 50μm. N = 6.

Mentions: To analyze if bone fracture before stroke increases neuroinflammation, we quantified CD68+ cells in the peri-infarct cortex (Fig 5A). We also used CCR2RFP/+CX3CR1GFP/+ mice to identify bone marrow-derived macrophages and local microglia. We found that bone fracture 6 hours before stroke increased the number of CD68+ cells in the peri-infarct regions (33.4±7.62% of total DAPI positive nuclei) compared to the stroke-only group (21.80±4.27%, p = 0.004, Fig 5B & 5C).


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 CD68+ macrophages in the peri-infarct region.(A) Image illustrates infarct core (Core), infarct border (dotted line) and the peri-infarct region (P.I.). (B) Quantification of CD68+ cells. *: P = 0.004, compared to stroke-only group. (C) Representative images of anti-CD68 antibody-stained sections. BF + 6hS: mice that received tibia fracture 6 hours before pMCAO; BF+1dS: mice that received tibia fracture 24 hours before pMCAO. Scale bars: 50μm. N = 6.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4835054&req=5

pone.0153835.g005: Bone fracture increased CD68+ macrophages in the peri-infarct region.(A) Image illustrates infarct core (Core), infarct border (dotted line) and the peri-infarct region (P.I.). (B) Quantification of CD68+ cells. *: P = 0.004, compared to stroke-only group. (C) Representative images of anti-CD68 antibody-stained sections. BF + 6hS: mice that received tibia fracture 6 hours before pMCAO; BF+1dS: mice that received tibia fracture 24 hours before pMCAO. Scale bars: 50μm. N = 6.
Mentions: To analyze if bone fracture before stroke increases neuroinflammation, we quantified CD68+ cells in the peri-infarct cortex (Fig 5A). We also used CCR2RFP/+CX3CR1GFP/+ mice to identify bone marrow-derived macrophages and local microglia. We found that bone fracture 6 hours before stroke increased the number of CD68+ cells in the peri-infarct regions (33.4±7.62% of total DAPI positive nuclei) compared to the stroke-only group (21.80±4.27%, p = 0.004, Fig 5B & 5C).

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