Hammond, Matthew D. and Taylor, Roslyn A. and Mullen, Michael T. and Ai, Youxi and Aguila, Hector L. and Mack, Matthias and Kasner, Scott E. and McCullough, Louise D. and Sansing, Lauren H. (2014) CCR2(+)Ly6C(hi) Inflammatory Monocyte Recruitment Exacerbates Acute Disability Following Intracerebral Hemorrhage. JOURNAL OF NEUROSCIENCE, 34 (11). pp. 3901-3909. ISSN 0270-6474,
Full text not available from this repository. (Request a copy)Abstract
Intracerebral hemorrhage (ICH) is a devastating type of stroke that lacks a specific treatment. An intense immune response develops after ICH, which contributes to neuronal injury, disability, and death. However, the specific mediators of inflammation-induced injury remain unclear. The objective of the present study was to determine whether blood-derived CCR2(+)Ly6C(hi) inflammatory monocytes contribute to disability. ICH was induced in mice and the resulting inflammatory response was quantified using flow cytometry, confocal microscopy, and neurobehavioral testing. Importantly, blood-derived monocytes were distinguished from resident microglia by differential CD45 staining and by using bone marrow chimeras with fluorescent leukocytes. After ICH, blood-derived CCR2(+)Ly6C(hi) inflammatory monocytes trafficked into the brain, outnumbered other leukocytes, and produced tumor necrosis factor. Ccr2(-/-) mice, which have few circulating inflammatory monocytes, exhibited better motor function following ICH than control mice. Chimeric mice with wild-type CNS cells and Ccr2(-/-) hematopoietic cells also exhibited early improvement in motor function, as did wild-type mice after inflammatory monocyte depletion. These findings suggest that blood-derived inflammatory monocytes contribute to acute neurological disability. To determine the translational relevance of our experimental findings, we examined CCL2, the principle ligand for the CCR2 receptor, in ICH patients. Serum samples from 85 patients were collected prospectively at two hospitals. In patients, higher CCL2 levels at 24 h were independently associated with poor functional outcome at day 7 after adjusting for potential confounding variables. Together, these findings suggest that inflammatory monocytes worsen early disability after murine ICH and may represent a therapeutic target for patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; CHEMOKINE RECEPTOR; BONE-MARROW; MOLECULAR SIGNATURES; ENDOTHELIAL-CELLS; BRAIN-INJURY; IN-VIVO; MICE; CCR2; EXPRESSION; bone marrow chimeras; CCL2; CCR2; intracerebral hemorrhage; monocytes; neuroinflammation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Nov 2019 09:03 |
| Last Modified: | 18 Nov 2019 09:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10472 |
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