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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 before pMCAO increased infarct volume.(A) Representative images of cresyl violet-stained brain sections. Scale bar: 1mm μm. (B) Quantification of infarct volume. *: P = 0.05 compared to stroke group, $: P<0.001: compared to stroke group; #: P<0.05, compared to bone fracture 24 hours before pMCAO group. n = 10 in stroke and tibia fracture 6 hours before stroke group. n = 9 in tibia fracture 24 hours before stroke group. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h Stroke: tibia fracture 24 hours before pMCAO.
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pone.0153835.g002: Bone fracture before pMCAO increased infarct volume.(A) Representative images of cresyl violet-stained brain sections. Scale bar: 1mm μm. (B) Quantification of infarct volume. *: P = 0.05 compared to stroke group, $: P<0.001: compared to stroke group; #: P<0.05, compared to bone fracture 24 hours before pMCAO group. n = 10 in stroke and tibia fracture 6 hours before stroke group. n = 9 in tibia fracture 24 hours before stroke group. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h Stroke: tibia fracture 24 hours before pMCAO.

Mentions: We found in our previous study that bone fracture one day after ischemic stroke exacerbates brain injury [9,12]. To determine if bone fracture before stroke has any influence on ischemic brain injury, we performed tibia fracture on mice 6 or 24 hours before pMCAO and analyzed infarct volume and neuron apoptosis. Compared to mice subjected to pMCAO (15.4±5.99 mm3) only, infarct volume increased in mice subjected to bone fracture before pMCAO (Fig 2). Tibia fracture 6 hours before stroke was 28.1±8.89 mm3 (p<0.001); tibia fracture 24 hours before stroke was 21.8±2.82 mm3 (p< 0.05). The infarct volumes in mice that received pMCAO 6 hours after bone fracture were also larger than those that received pMCAO 24 hours after (p<0.05).


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 before pMCAO increased infarct volume.(A) Representative images of cresyl violet-stained brain sections. Scale bar: 1mm μm. (B) Quantification of infarct volume. *: P = 0.05 compared to stroke group, $: P<0.001: compared to stroke group; #: P<0.05, compared to bone fracture 24 hours before pMCAO group. n = 10 in stroke and tibia fracture 6 hours before stroke group. n = 9 in tibia fracture 24 hours before stroke group. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h Stroke: tibia fracture 24 hours before pMCAO.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4835054&req=5

pone.0153835.g002: Bone fracture before pMCAO increased infarct volume.(A) Representative images of cresyl violet-stained brain sections. Scale bar: 1mm μm. (B) Quantification of infarct volume. *: P = 0.05 compared to stroke group, $: P<0.001: compared to stroke group; #: P<0.05, compared to bone fracture 24 hours before pMCAO group. n = 10 in stroke and tibia fracture 6 hours before stroke group. n = 9 in tibia fracture 24 hours before stroke group. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h Stroke: tibia fracture 24 hours before pMCAO.
Mentions: We found in our previous study that bone fracture one day after ischemic stroke exacerbates brain injury [9,12]. To determine if bone fracture before stroke has any influence on ischemic brain injury, we performed tibia fracture on mice 6 or 24 hours before pMCAO and analyzed infarct volume and neuron apoptosis. Compared to mice subjected to pMCAO (15.4±5.99 mm3) only, infarct volume increased in mice subjected to bone fracture before pMCAO (Fig 2). Tibia fracture 6 hours before stroke was 28.1±8.89 mm3 (p<0.001); tibia fracture 24 hours before stroke was 21.8±2.82 mm3 (p< 0.05). The infarct volumes in mice that received pMCAO 6 hours after bone fracture were also larger than those that received pMCAO 24 hours after (p<0.05).

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