Blood cell-derived RANTES mediates cerebral microvascular dysfunction, inflammation, and tissue injury after focal ischemia-reperfusion.

Abstract:

BACKGROUND AND PURPOSE:Although chemokines have been implicated in cardiovascular diseases, few studies have addressed the role of these inflammatory mediators in ischemic stroke. This study tested the hypothesis that RANTES (CCL5; regulated on activation, normal T-cell expressed and secreted) mediates the cerebral microvascular dysfunction, inflammation, and tissue injury induced by brain ischemia and reperfusion. METHODS:After 60-minute middle cerebral artery occlusion and reperfusion, the adhesion of leukocytes and platelets in cerebral venules, infarct volume, and blood-brain barrier permeability were measured in wild-type mice (WT), RANTES-deficient mice (RANTES(-/-)), WT mice transplanted with RANTES(-/-) bone marrow (RANTES>WT), and control bone marrow chimeras (WT>WT). The concentration of RANTES and several cytokines was also measured by enzyme-linked immunosorbent assay and a cytometric bead array. RESULTS:The enhanced leukocyte and platelet adhesion, increased blood-brain barrier permeability, and tissue infarction elicited in WT and WT>WT mice after middle cerebral artery occlusion and reperfusion were significantly blunted in RANTES(-/-) mice. Similar attenuation of the middle cerebral artery occlusion and reperfusion-induced responses were noted in RANTES>WT chimeras. Although RANTES deficiency did not alter the changes in tissue cytokine levels elicited by middle cerebral artery occlusion and reperfusion, plasma concentrations interleukin-6, interleukin-10, and interleukin-12 were all reduced. CONCLUSIONS:These findings implicate blood cell-derived RANTES in the microvascular, inflammatory, and tissue injury responses of the brain to ischemia and reperfusion.

journal_name

Stroke

journal_title

Stroke

authors

Terao S,Yilmaz G,Stokes KY,Russell J,Ishikawa M,Kawase T,Granger DN

doi

10.1161/STROKEAHA.107.513150

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

2560-70

issue

9

eissn

0039-2499

issn

1524-4628

pii

STROKEAHA.107.513150

journal_volume

39

pub_type

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