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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

Experimental design.Time course for group with bone fracture (A) 6 hours before pMCAO, and (B) 24 hours before pMCAO. All mice underwent behavioral training 4 days before bone fracture, and baseline behavior performance was collected 1 day before bone fracture. Bone fracture was performed at day 0 (D0). Behavioral tests were performed 3 days after pMCAO. Brain samples were collected after the behavioral test. TF: tibia fracture.
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pone.0153835.g001: Experimental design.Time course for group with bone fracture (A) 6 hours before pMCAO, and (B) 24 hours before pMCAO. All mice underwent behavioral training 4 days before bone fracture, and baseline behavior performance was collected 1 day before bone fracture. Bone fracture was performed at day 0 (D0). Behavioral tests were performed 3 days after pMCAO. Brain samples were collected after the behavioral test. TF: tibia fracture.

Mentions: C57BL/6J male mice (WT) were purchased from the Jackson Laboratory (Bar Harbor, ME, USA). Ccr2/RFP/+/Cx3cr1/GFP/+ transgenic mice that have red fluorescent protein gene knocked into one allele of C-C motif Chemokine receptor-2 (Ccr2RFP/+) and green fluorescent protein gene knocked into one allele of Cx3cr1 (Cx3cr1GFP/+) mice [11] were provided by Israel F. Charo at the University of California, San Francisco. Fifty-six 10 to 12-week-old WT mice and 30 10 to 12-week-old Ccr2/RFP/+/Cx3cr1GFP/+ mice were randomly assigned to 5 groups (Table 1). Fig 1 shows the experimental design. Researchers, blinded to the group assignment, performed neurobehavioral tests, infarct volume measurement, and cell counting.


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)

Experimental design.Time course for group with bone fracture (A) 6 hours before pMCAO, and (B) 24 hours before pMCAO. All mice underwent behavioral training 4 days before bone fracture, and baseline behavior performance was collected 1 day before bone fracture. Bone fracture was performed at day 0 (D0). Behavioral tests were performed 3 days after pMCAO. Brain samples were collected after the behavioral test. TF: tibia fracture.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0153835.g001: Experimental design.Time course for group with bone fracture (A) 6 hours before pMCAO, and (B) 24 hours before pMCAO. All mice underwent behavioral training 4 days before bone fracture, and baseline behavior performance was collected 1 day before bone fracture. Bone fracture was performed at day 0 (D0). Behavioral tests were performed 3 days after pMCAO. Brain samples were collected after the behavioral test. TF: tibia fracture.
Mentions: C57BL/6J male mice (WT) were purchased from the Jackson Laboratory (Bar Harbor, ME, USA). Ccr2/RFP/+/Cx3cr1/GFP/+ transgenic mice that have red fluorescent protein gene knocked into one allele of C-C motif Chemokine receptor-2 (Ccr2RFP/+) and green fluorescent protein gene knocked into one allele of Cx3cr1 (Cx3cr1GFP/+) mice [11] were provided by Israel F. Charo at the University of California, San Francisco. Fifty-six 10 to 12-week-old WT mice and 30 10 to 12-week-old Ccr2/RFP/+/Cx3cr1GFP/+ mice were randomly assigned to 5 groups (Table 1). Fig 1 shows the experimental design. Researchers, blinded to the group assignment, performed neurobehavioral tests, infarct volume measurement, and cell counting.

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