title: Evidence of CCR2-independent transmigration of Ly6C(hi) monocytes into the brain after permanent cerebral ischemia in mice.
abstract: Previously we showed that INCB3344, a CCR2 antagonist, inhibits transmigration of Ly6C(hi) monocytes into the brain after ischemia-reperfusion. Here we tested the effect of CCR2 inhibition during permanent cerebral ischemia. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (30 or 100mg/kg IP) 1h before middle cerebral artery occlusion and at 2 and 6h after the initiation of ischemia. After 24h, we assessed functional outcome, infarct volume and quantified immune cells in blood and brain. The increase in circulating bone marrow-derived Ly6C(hi) monocytes, but not the infiltration of those cells into the brain, was blocked by the CCR2 antagonist. INCB3344 had no effect on either neurological deficit or infarct volume. Our data confirm that cerebral ischemia triggers a CCR2-dependent increase in circulating Ly6C(hi) monocytes, but suggest that in the absence of reperfusion these cells may transmigrate into the ischemic brain in a CCR2-independent manner.
authors.affiliation: Vascular Biology and Immunopharmacology Group, Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
authors.forename: Hannah X
authors.initials: HX
authors.lastname: Chu
authors.affiliation: Vascular Biology and Immunopharmacology Group, Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
authors.affiliation: Vascular Biology and Immunopharmacology Group, Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
authors.forename: Seyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Vascular Biology and Immunopharmacology Group, Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
authors.forename: Brad R S
authors.initials: BRS
authors.lastname: Broughton
authors.affiliation: Vascular Biology and Immunopharmacology Group, Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Drummond
authors.affiliation: Vascular Biology and Immunopharmacology Group, Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia. Electronic address: chris.sobey@monash.edu.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000276:immunology / Q000503:physiopathology; D002545:Brain Ischemia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D011759:Pyrrolidines / Q000494:pharmacology; D011897:Random Allocation; D054390:Receptors, CCR2 / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; C515335:Ccr2 protein, mouse; C505875:INCB3344; C494192:Ly-6C antigen, mouse; D011759:Pyrrolidines; D054390:Receptors, CCR2
keywords: CCR2 antagonist; Inflammation; Ly6C(hi) monocytes; Permanent cerebral ischemia; Stroke