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Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice

Stroke (1970), 2007-04, Vol.38 (4), p.1345-1353 [Peer Reviewed Journal]

2007 INIST-CNRS ;ISSN: 0039-2499 ;EISSN: 1524-4628 ;DOI: 10.1161/01.STR.0000259709.16654.8f ;PMID: 17332467 ;CODEN: SJCCA7

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Title:
Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice
Author: DIMITRIJEVIC, Oliver B ; STAMATOVIC, Svetlana M ; KEEP, Richard F ; ANDJELKOVIC, Anuska V
Subjects: Animals ; Biological and medical sciences ; Blood-Brain Barrier - immunology ; Blood-Brain Barrier - physiopathology ; Brain Edema - genetics ; Brain Edema - immunology ; Brain Edema - physiopathology ; Brain Infarction - genetics ; Brain Infarction - immunology ; Brain Infarction - physiopathology ; Brain Ischemia - genetics ; Brain Ischemia - immunology ; Brain Ischemia - physiopathology ; Chemokine CCL2 - immunology ; Chemotaxis, Leukocyte - genetics ; Chemotaxis, Leukocyte - immunology ; Cytokines - immunology ; Cytokines - secretion ; Cytoprotection - genetics ; Cytoprotection - immunology ; Down-Regulation - genetics ; Down-Regulation - immunology ; Encephalitis - genetics ; Encephalitis - immunology ; Encephalitis - physiopathology ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes - immunology ; Monocytes - secretion ; Nervous system (semeiology, syndromes) ; Neurology ; Neuropharmacology ; Neuroprotective agent ; Neutrophils - immunology ; Neutrophils - secretion ; Pharmacology. Drug treatments ; Receptors, CCR2 ; Receptors, Chemokine - genetics ; Reperfusion Injury - genetics ; Reperfusion Injury - immunology ; Reperfusion Injury - physiopathology ; Vascular diseases and vascular malformations of the nervous system
Is Part Of: Stroke (1970), 2007-04, Vol.38 (4), p.1345-1353
Description: The chemokine, monocyte chemoattractant protein-1 (CCL2), is a major factor driving leukocyte infiltration into the brain parenchyma in a variety of neuropathologic conditions associated with inflammation, including stroke. In addition, recent studies indicate that CCL2 and its receptor (CCR2) could have an important role in regulating blood-brain barrier (BBB) permeability. This study evaluated the role of the CCL2/CCR2 axis in regulating postischemic inflammation, BBB breakdown, and vasogenic edema formation. CCR2(-/-) and CCR2(+/+) mice were subjected to focal transient cerebral ischemia. BBB permeability and brain edema formation were observed at days 1 and 5 of reperfusion by evaluating the product surface area for fluorescein isothiocyanate-albumin and measuring water and electrolyte contents. Immunohistochemistry was used to assess leukocyte infiltration. cDNA gene and protein arrays for inflammatory cytokines were used to assess inflammatory profiles in CCR2(+/+) and CCR2(-/-) mice. CCR2(-/-) mice had reduced infarct sizes and significantly reduced BBB permeability and brain edema formation in the affected ischemic hemisphere compared with CCR2(+/+) mice. This reduction in injury was closely associated with reduced infiltration of not only monocytes but also neutrophils (7- and 4-fold decreases, respectively). In addition, CCR2(-/-) mice had reduced expression/production of inflammatory cytokines during reperfusion. These data suggest that inhibiting the CCL2/CCR2 axis affects brain reperfusion outcome by reducing brain edema, leukocyte infiltration, and inflammatory mediator expression.
Publisher: Hagerstown, MD: Lippincott Williams & Wilkins
Language: English
Identifier: ISSN: 0039-2499
EISSN: 1524-4628
DOI: 10.1161/01.STR.0000259709.16654.8f
PMID: 17332467
CODEN: SJCCA7
Source: MEDLINE
Alma/SFX Local Collection

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Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice

2007 INIST-CNRS ;ISSN: 0039-2499 ;EISSN: 1524-4628 ;DOI: 10.1161/01.STR.0000259709.16654.8f ;PMID: 17332467 ;CODEN: SJCCA7

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