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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 behavioral deficits.(A) Adhesive removal test (right paw). Mice that received bone fracture took longer to remove adhesive from right paw. #: P<0.001 compared to stroke-only mice. *: P = 0.05: compared to stroke-only group. & = 0.02 compared to mice that received tibia fracture 24 hours before pMCAO. (B) Adhesive removal test (left paw). n = 10 for control groups (BF+3-day, BF+4day) that received tibia fracture and sham pMCAO, and had their behavioral test done 3 or 4 days after bone fracture. (C) Corner test. #: P = 0.001 compared to stroke group; *:P = 0.035 compared to stroke group. n = 10 for control groups (BF+3-day, BF+4day) that received tibia fracture and sham pMCAO, and had their behavioral test done 3 or 4 days after bone fracture. n = 10 for pMCAO-only group. n = 12 for groups that received bone fracture 6 hours or 24 hours before pMCAO. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h stroke: tibia fracture 24 hours before pMCAO.
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pone.0153835.g004: Bone fracture before pMCAO increased behavioral deficits.(A) Adhesive removal test (right paw). Mice that received bone fracture took longer to remove adhesive from right paw. #: P<0.001 compared to stroke-only mice. *: P = 0.05: compared to stroke-only group. & = 0.02 compared to mice that received tibia fracture 24 hours before pMCAO. (B) Adhesive removal test (left paw). n = 10 for control groups (BF+3-day, BF+4day) that received tibia fracture and sham pMCAO, and had their behavioral test done 3 or 4 days after bone fracture. (C) Corner test. #: P = 0.001 compared to stroke group; *:P = 0.035 compared to stroke group. n = 10 for control groups (BF+3-day, BF+4day) that received tibia fracture and sham pMCAO, and had their behavioral test done 3 or 4 days after bone fracture. n = 10 for pMCAO-only group. n = 12 for groups that received bone fracture 6 hours or 24 hours before pMCAO. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h stroke: tibia fracture 24 hours before pMCAO.

Mentions: To test if bone fracture before pMCAO increases behavioral dysfunction, we performed adhesive removal and corner tests on mice 3 days after pMCAO. To match the tibia fracture time, we included two groups of mice that were subjected to tibia fracture only in the tests. One group had behavioral tests before and 3 days after the fracture, which was used as control for the group subjected to pMCAO 6 hours after tibia fracture. The other group was tested before and 4 days after tibia fracture, which was used as control of the group subjected to pMCAO 24 hours after tibia fracture. We found that compared to stroke-only mice (29±6.8 seconds), those subjected to bone fracture and pMCAO took longer to remove the sticker from the right forepaw (Fig 4A): bone fracture 6 hours before pMCAO group, 52±14.5 seconds, p<0.001; bone fracture 24 hours before pMCAO, 40±12.2 seconds, p = 0.05. The mice subjected to bone fracture 6 hours before pMCAO also took a longer time than those that received bone fracture 24 hours before pMCAO (p = 0.02). The time it took to remove the adhesive from the left paw was similar among all the groups (p>0.05, Fig 4B).


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 behavioral deficits.(A) Adhesive removal test (right paw). Mice that received bone fracture took longer to remove adhesive from right paw. #: P<0.001 compared to stroke-only mice. *: P = 0.05: compared to stroke-only group. & = 0.02 compared to mice that received tibia fracture 24 hours before pMCAO. (B) Adhesive removal test (left paw). n = 10 for control groups (BF+3-day, BF+4day) that received tibia fracture and sham pMCAO, and had their behavioral test done 3 or 4 days after bone fracture. (C) Corner test. #: P = 0.001 compared to stroke group; *:P = 0.035 compared to stroke group. n = 10 for control groups (BF+3-day, BF+4day) that received tibia fracture and sham pMCAO, and had their behavioral test done 3 or 4 days after bone fracture. n = 10 for pMCAO-only group. n = 12 for groups that received bone fracture 6 hours or 24 hours before pMCAO. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h stroke: tibia fracture 24 hours before pMCAO.
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pone.0153835.g004: Bone fracture before pMCAO increased behavioral deficits.(A) Adhesive removal test (right paw). Mice that received bone fracture took longer to remove adhesive from right paw. #: P<0.001 compared to stroke-only mice. *: P = 0.05: compared to stroke-only group. & = 0.02 compared to mice that received tibia fracture 24 hours before pMCAO. (B) Adhesive removal test (left paw). n = 10 for control groups (BF+3-day, BF+4day) that received tibia fracture and sham pMCAO, and had their behavioral test done 3 or 4 days after bone fracture. (C) Corner test. #: P = 0.001 compared to stroke group; *:P = 0.035 compared to stroke group. n = 10 for control groups (BF+3-day, BF+4day) that received tibia fracture and sham pMCAO, and had their behavioral test done 3 or 4 days after bone fracture. n = 10 for pMCAO-only group. n = 12 for groups that received bone fracture 6 hours or 24 hours before pMCAO. BF 6h Stroke: tibia fracture 6 hours before pMCAO; BF 24h stroke: tibia fracture 24 hours before pMCAO.
Mentions: To test if bone fracture before pMCAO increases behavioral dysfunction, we performed adhesive removal and corner tests on mice 3 days after pMCAO. To match the tibia fracture time, we included two groups of mice that were subjected to tibia fracture only in the tests. One group had behavioral tests before and 3 days after the fracture, which was used as control for the group subjected to pMCAO 6 hours after tibia fracture. The other group was tested before and 4 days after tibia fracture, which was used as control of the group subjected to pMCAO 24 hours after tibia fracture. We found that compared to stroke-only mice (29±6.8 seconds), those subjected to bone fracture and pMCAO took longer to remove the sticker from the right forepaw (Fig 4A): bone fracture 6 hours before pMCAO group, 52±14.5 seconds, p<0.001; bone fracture 24 hours before pMCAO, 40±12.2 seconds, p = 0.05. The mice subjected to bone fracture 6 hours before pMCAO also took a longer time than those that received bone fracture 24 hours before pMCAO (p = 0.02). The time it took to remove the adhesive from the left paw was similar among all the groups (p>0.05, Fig 4B).

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