Document Detail


Macrophages prevent hemorrhagic infarct transformation in murine stroke models.
MedLine Citation:
PMID:  22718543     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Inflammation is increasingly viewed as a new therapeutic target in subacute stages of brain infarction. However, apart from causing secondary damage, inflammation could equally promote beneficial lesion remodeling and repair. Distinct subpopulations of monocytes/macrophages (MOs/MPs) may critically determine the outcome of lesion-associated inflammation.
METHODS: We addressed the role of bone marrow-derived MOs/MPs in 2 different mouse models of ischemic stroke using a combined cell-specific depletion, chemokine receptor knockout, bone marrow chimeric, and pharmacological approach.
RESULTS: Starting within 24 hours of stroke onset, immature Ly6c(hi) monocytes infiltrated into the infarct border zone and differentiated into mature Ly6c(lo) phagocytes within the lesion compartment. MO/MP infiltration was CCR2-dependent, whereas we did not obtain evidence for additional recruitment via CX3CR1. Depletion of circulating MOs/MPs or selective targeting of CCR2 in bone marrow-derived cells caused delayed clinical deterioration and hemorrhagic conversion of the infarctions. Bleeding frequently occurred around thin-walled, dilated neovessels in the infarct border zone and was accompanied by decreased expression of transforming growth factor (TGF)-β1 and collagen-4, along with diminished activation of Smad2. Injection of TGF-β1 into the lesion border zone greatly reduced infarct bleeding in MO/MP-depleted mice.
INTERPRETATION: Bone marrow-derived MOs/MPs recruited via CCR2 and acting via TGF-β1 are essential for maintaining integrity of the neurovascular unit following brain ischemia. Future therapies should be aimed at enhancing physiological repair functions of CCR2(+) MOs/MPs rather than blocking their hematogenous recruitment.
Authors:
Michael Gliem; Anne Kathrin Mausberg; John-Ih Lee; Ioannis Simiantonakis; Nico van Rooijen; Hans-Peter Hartung; Sebastian Jander
Related Documents :
16891293 - Lack of deleterious interaction between angiotensin receptor blockers and beta-blockers...
22660923 - Heart failure with a normal ejection fraction: treatments for a complex syndrome?
9140603 - Directional atherectomy and balloon angioplasty for lower extremity arterial disease.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of neurology     Volume:  71     ISSN:  1531-8249     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-21     Completed Date:  2012-08-30     Revised Date:  2013-01-28    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  743-52     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 American Neurological Association.
Affiliation:
Departments of Neurology, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Düsseldorf, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / metabolism
Antigens, CD11b / genetics,  metabolism
Antigens, CD45 / genetics
Antigens, Differentiation, Myelomonocytic / metabolism
Antigens, Ly / metabolism
Brain Infarction / etiology,  prevention & control*
Cell Differentiation
Diphtheria Toxin / administration & dosage
Disease Models, Animal
Drug Administration Routes
Flow Cytometry
Gene Expression Regulation / drug effects,  genetics,  physiology*
Infarction, Middle Cerebral Artery / complications
Intercellular Signaling Peptides and Proteins / metabolism
Interferon Inducers / administration & dosage
Intracranial Hemorrhages / etiology,  prevention & control*
Intracranial Thrombosis / complications
Macrophages / physiology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Motor Activity / physiology
Organometallic Compounds / administration & dosage
Receptors, CCR2 / deficiency
Receptors, Chemokine / genetics
Stroke / complications*,  etiology,  pathology*
Time Factors
Transforming Growth Factor beta1 / administration & dosage,  metabolism
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD11b; 0/Antigens, Differentiation, Myelomonocytic; 0/Antigens, Ly; 0/CD68 antigen, human; 0/Ccr2 protein, mouse; 0/Cx3cr1 protein, mouse; 0/Diphtheria Toxin; 0/Intercellular Signaling Peptides and Proteins; 0/Interferon Inducers; 0/Organometallic Compounds; 0/Receptors, CCR2; 0/Receptors, Chemokine; 0/Transforming Growth Factor beta1; 149176-25-0/heparin-binding EGF-like growth factor; 1Q2P9TO9Q7/proxigermanium; EC 3.1.3.48/Antigens, CD45; EC 3.1.3.48/Ptprc protein, mouse
Comments/Corrections
Comment In:
Ann Neurol. 2012 Jun;71(6):729-31   [PMID:  22718541 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Comparative effectiveness and implementation research: directions for neurology.
Next Document:  CD36 in the periphery and brain synergizes in stroke injury in hyperlipidemia.