Evidence of CCR2-independent transmigration of Ly6Chi monocytes into the brain after permanent cerebral ischemia in mice

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Previously we showed that INCB3344, a CCR2 antagonist, inhibits transmigration of Ly6Chi 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 100 mg/kg IP) 1 h before middle cerebral artery occlusion and at 2 and 6 h after the initiation of ischemia. After 24 h, we assessed functional outcome, infarct volume and quantified immune cells in blood and brain. The increase in circulating bone marrow-derived Ly6Chi 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 Ly6Chi monocytes, but suggest that in the absence of reperfusion these cells may transmigrate into the ischemic brain in a CCR2-independent manner.
Original languageEnglish
Pages (from-to)118-127
Number of pages10
JournalBrain Research
Volume1637
DOIs
Publication statusPublished - 15 Apr 2016

Keywords

  • CCR2 antagonist
  • inflammation
  • Ly6Chi monocytes
  • permanent cerebral ischemia
  • stroke

Cite this

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title = "Evidence of CCR2-independent transmigration of Ly6Chi monocytes into the brain after permanent cerebral ischemia in mice",
abstract = "Previously we showed that INCB3344, a CCR2 antagonist, inhibits transmigration of Ly6Chi 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 100 mg/kg IP) 1 h before middle cerebral artery occlusion and at 2 and 6 h after the initiation of ischemia. After 24 h, we assessed functional outcome, infarct volume and quantified immune cells in blood and brain. The increase in circulating bone marrow-derived Ly6Chi 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 Ly6Chi monocytes, but suggest that in the absence of reperfusion these cells may transmigrate into the ischemic brain in a CCR2-independent manner.",
keywords = "CCR2 antagonist, inflammation, Ly6Chi monocytes, permanent cerebral ischemia, stroke",
author = "Chu, {Hannah X.} and Kim, {Hyun Ah} and Seyoung Lee and Broughton, {Brad R.S.} and Drummond, {Grant R.} and Sobey, {Christopher G.}",
year = "2016",
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doi = "10.1016/j.brainres.2016.02.030",
language = "English",
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pages = "118--127",
journal = "Brain Research",
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Evidence of CCR2-independent transmigration of Ly6Chi monocytes into the brain after permanent cerebral ischemia in mice. / Chu, Hannah X.; Kim, Hyun Ah; Lee, Seyoung; Broughton, Brad R.S.; Drummond, Grant R.; Sobey, Christopher G.

In: Brain Research, Vol. 1637, 15.04.2016, p. 118-127.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Evidence of CCR2-independent transmigration of Ly6Chi monocytes into the brain after permanent cerebral ischemia in mice

AU - Chu, Hannah X.

AU - Kim, Hyun Ah

AU - Lee, Seyoung

AU - Broughton, Brad R.S.

AU - Drummond, Grant R.

AU - Sobey, Christopher G.

PY - 2016/4/15

Y1 - 2016/4/15

N2 - Previously we showed that INCB3344, a CCR2 antagonist, inhibits transmigration of Ly6Chi 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 100 mg/kg IP) 1 h before middle cerebral artery occlusion and at 2 and 6 h after the initiation of ischemia. After 24 h, we assessed functional outcome, infarct volume and quantified immune cells in blood and brain. The increase in circulating bone marrow-derived Ly6Chi 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 Ly6Chi monocytes, but suggest that in the absence of reperfusion these cells may transmigrate into the ischemic brain in a CCR2-independent manner.

AB - Previously we showed that INCB3344, a CCR2 antagonist, inhibits transmigration of Ly6Chi 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 100 mg/kg IP) 1 h before middle cerebral artery occlusion and at 2 and 6 h after the initiation of ischemia. After 24 h, we assessed functional outcome, infarct volume and quantified immune cells in blood and brain. The increase in circulating bone marrow-derived Ly6Chi 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 Ly6Chi monocytes, but suggest that in the absence of reperfusion these cells may transmigrate into the ischemic brain in a CCR2-independent manner.

KW - CCR2 antagonist

KW - inflammation

KW - Ly6Chi monocytes

KW - permanent cerebral ischemia

KW - stroke

UR - http://www.ncbi.nlm.nih.gov/pubmed/26921777

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