Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia

Hannah X Chu, Kim Huynh, Seyoung Sandy Lee, Jeffrey P Moore, Christopher T L Chan, Antony Vinh, Mathias Gelderblom, Thiruma Arumugam, Bradley R S Broughton, Grant R Drummond, Christopher G Sobey

Research output: Contribution to journalArticleResearchpeer-review

Abstract

We tested whether significant leukocyte infiltration occurs in a mouse model of permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or 24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral artery occlusion (MCAO). Using flow cytometry, we observed approximately 15,000 leukocytes (CD45(+high) cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising approximately 40 lymphoid cells and approximately 60 myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to approximately 5,000 as early as 3 hours after pMCAO. Several cell types (monocytes, macrophages, B lymphocytes, CD8(+) T lymphocytes, and natural killer cells) were also increased at 3 hours to levels sustained for 24 hours, whereas others (CD4(+) T cells, natural killer T cells, and dendritic cells) were unchanged at 3 hours, but were increased by 24 hours after pMCAO. Immunohistochemical analysis revealed that leukocytes typically had entered and widely dispersed throughout the parenchyma of the infarct within 3 hours. Moreover, compared with pMCAO, there were approximately 50 fewer infiltrating leukocytes at 24 hours after transient MCAO (tMCAO), independent of infarct size. Microglial cell numbers were bilaterally increased in both models. These findings indicate that a profound infiltration of inflammatory cells occurs in the brain early after focal ischemia, especially without reperfusion.
Original languageEnglish
Pages (from-to)450 - 459
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume34
Issue number3
DOIs
Publication statusPublished - 2014

Cite this

Chu, Hannah X ; Huynh, Kim ; Lee, Seyoung Sandy ; Moore, Jeffrey P ; Chan, Christopher T L ; Vinh, Antony ; Gelderblom, Mathias ; Arumugam, Thiruma ; Broughton, Bradley R S ; Drummond, Grant R ; Sobey, Christopher G. / Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia. In: Journal of Cerebral Blood Flow and Metabolism. 2014 ; Vol. 34, No. 3. pp. 450 - 459.
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abstract = "We tested whether significant leukocyte infiltration occurs in a mouse model of permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or 24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral artery occlusion (MCAO). Using flow cytometry, we observed approximately 15,000 leukocytes (CD45(+high) cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising approximately 40 lymphoid cells and approximately 60 myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to approximately 5,000 as early as 3 hours after pMCAO. Several cell types (monocytes, macrophages, B lymphocytes, CD8(+) T lymphocytes, and natural killer cells) were also increased at 3 hours to levels sustained for 24 hours, whereas others (CD4(+) T cells, natural killer T cells, and dendritic cells) were unchanged at 3 hours, but were increased by 24 hours after pMCAO. Immunohistochemical analysis revealed that leukocytes typically had entered and widely dispersed throughout the parenchyma of the infarct within 3 hours. Moreover, compared with pMCAO, there were approximately 50 fewer infiltrating leukocytes at 24 hours after transient MCAO (tMCAO), independent of infarct size. Microglial cell numbers were bilaterally increased in both models. These findings indicate that a profound infiltration of inflammatory cells occurs in the brain early after focal ischemia, especially without reperfusion.",
author = "Chu, {Hannah X} and Kim Huynh and Lee, {Seyoung Sandy} and Moore, {Jeffrey P} and Chan, {Christopher T L} and Antony Vinh and Mathias Gelderblom and Thiruma Arumugam and Broughton, {Bradley R S} and Drummond, {Grant R} and Sobey, {Christopher G}",
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Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia. / Chu, Hannah X; Huynh, Kim; Lee, Seyoung Sandy; Moore, Jeffrey P; Chan, Christopher T L; Vinh, Antony; Gelderblom, Mathias; Arumugam, Thiruma; Broughton, Bradley R S; Drummond, Grant R; Sobey, Christopher G.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 34, No. 3, 2014, p. 450 - 459.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia

AU - Chu, Hannah X

AU - Huynh, Kim

AU - Lee, Seyoung Sandy

AU - Moore, Jeffrey P

AU - Chan, Christopher T L

AU - Vinh, Antony

AU - Gelderblom, Mathias

AU - Arumugam, Thiruma

AU - Broughton, Bradley R S

AU - Drummond, Grant R

AU - Sobey, Christopher G

PY - 2014

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N2 - We tested whether significant leukocyte infiltration occurs in a mouse model of permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or 24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral artery occlusion (MCAO). Using flow cytometry, we observed approximately 15,000 leukocytes (CD45(+high) cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising approximately 40 lymphoid cells and approximately 60 myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to approximately 5,000 as early as 3 hours after pMCAO. Several cell types (monocytes, macrophages, B lymphocytes, CD8(+) T lymphocytes, and natural killer cells) were also increased at 3 hours to levels sustained for 24 hours, whereas others (CD4(+) T cells, natural killer T cells, and dendritic cells) were unchanged at 3 hours, but were increased by 24 hours after pMCAO. Immunohistochemical analysis revealed that leukocytes typically had entered and widely dispersed throughout the parenchyma of the infarct within 3 hours. Moreover, compared with pMCAO, there were approximately 50 fewer infiltrating leukocytes at 24 hours after transient MCAO (tMCAO), independent of infarct size. Microglial cell numbers were bilaterally increased in both models. These findings indicate that a profound infiltration of inflammatory cells occurs in the brain early after focal ischemia, especially without reperfusion.

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DO - 10.1038/jcbfm.2013.217

M3 - Article

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JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

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