title: Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia.
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 ∼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.
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors: Hannah X
authors: HX
authors: Chu
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors: Hyun Ah
authors: HA
authors: Kim
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors: Seyoung
authors: S
authors: Lee
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors: Jeffrey P
authors: JP
authors: Moore
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors: Christopher T
authors: CT
authors: Chan
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors: Antony
authors: A
authors: Vinh
authors: Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Mathias
authors: M
authors: Gelderblom
authors: Department of Pharmacology, University of Queensland, St Lucia, Queensland, Australia.
authors: Thiruma V
authors: TV
authors: Arumugam
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors: Brad R S
authors: BR
authors: Broughton
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors: Grant R
authors: GR
authors: Drummond
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors: Christopher G
authors: CG
authors: Sobey
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology*; D002546:Ischemic Attack, Transient / Q000276:immunology*; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology*; D013997:Time Factors