The CCL2-CCR2 system affects the progression and clearance of intracerebral hemorrhage

Yao Yao, Stella E. Tsirka

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Intracerebral hemorrhage (ICH) has been associated with inflammation and apoptosis. The CCL2-CCR2 chemotactic system is one of the major signaling pathways that induce inflammation and apoptosis. However, its role on ICH has not been investigated. We subjected wild-type, CCL2 -/-, and CCR2 -/- mice to collagenase-induced ICH, and assessed histological and behavioral outcomes. Lack of CCL2 or CCR2 decreased the hematoma volume early after collagenase-induced ICH but delayed its recovery. The hematoma size was accompanied by brain edema, neuronal death, and neurological scores. Although microglia activation/migration was attenuated in CCL2 -/- or CCR2 -/- mice 1 day after injury, more microglia were present at later time points, suggesting that alternative signaling pathways had been activated to recruit them. On the contrary, leukocyte and neutrophil infiltration were decreased in these mice, suggesting a tighter/recovered blood-brain barrier. In addition, we also found that FL- and K104Stop-CCL2 were able to restore the changes found in CCL2 -/- mice, but K104A-CCL2 failed to do so. These results suggest that plasmin-mediated truncation of CCL2 may be an indispensable step to fully activate the chemokine in vivo. The data also indicate that CCL2-CCR2 signaling pathway may be a molecular target for the treatment of ICH.

Original languageEnglish (US)
Pages (from-to)908-918
Number of pages11
JournalGlia
Volume60
Issue number6
DOIs
StatePublished - May 2012

Keywords

  • CCL2
  • CCR2
  • Intracerebral hemorrhage

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