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

TY - JOUR

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

AU - Chu, Hannah X

AU - Kim, Hyun Ah

AU - Lee, Seyoung

AU - Moore, Jeffrey P

AU - Chan, Christopher T

AU - Vinh, Antony

AU - Gelderblom, Mathias

AU - Arumugam, Thiruma V

AU - Broughton, Brad R S

AU - Drummond, Grant R

AU - Sobey, Christopher G

PY - 2014

Y1 - 2014

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 ∼15,000 leukocytes (CD45(+high) cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising ∼40% lymphoid cells and ∼60% myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to ∼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 ∼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.

AB - 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 ∼15,000 leukocytes (CD45(+high) cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising ∼40% lymphoid cells and ∼60% myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to ∼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 ∼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.

KW - Animals

KW - Chemotaxis, Leukocyte

KW - Disease Models, Animal

KW - Flow Cytometry

KW - Immunohistochemistry

KW - Infarction, Middle Cerebral Artery

KW - Ischemic Attack, Transient

KW - Leukocyte Count

KW - Lymphocyte Count

KW - Lymphocytes

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Neutrophil Infiltration

KW - Time Factors

U2 - 10.1038/jcbfm.2013.217

DO - 10.1038/jcbfm.2013.217

M3 - SCORING: Journal article

C2 - 24326388

VL - 34

SP - 450

EP - 459

JO - J CEREBR BLOOD F MET

JF - J CEREBR BLOOD F MET

SN - 0271-678X

IS - 3

ER -