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The cytokines TNF, MCP‐1 and CINC‐1 mediate diminished dilation of middle cerebral artery after ischemic stroke in rats (1068.2)
Author(s) -
Broskova Zuzana,
Anthony Daniel,
Bagi Zsolt
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1068.2
Subject(s) - medicine , dilator , middle cerebral artery , vasomotor , endocrinology , bradykinin , sodium nitroprusside , vasodilation , cerebral circulation , cerebral arteries , tumor necrosis factor alpha , proinflammatory cytokine , cytokine , vasoconstriction , inflammation , ischemia , nitric oxide , receptor
The level of inflammatory cytokines TNF, Monocyte Chemoattractant Protein (MCP‐1) and Cytokine‐Induced Neutrophil Chemoattractant (CINC‐1) is elevated after ischemic stroke (IS). The vasomotor effects of TNF, MCP‐1 and CINC‐1 on cerebral arteries have not yet been fully elucidated after IS. We aimed to evaluate the direct effect of these cytokines on MCA diameter under normal conditions and also after IS. In isolated, pressurized middle cerebral arteries (MCA) of normal Wistar rats, TNF, CINC‐1 (10‐14 ‐ 10‐11 M) and MCP‐1 (10‐16 ‐ 10‐13 M) elicited vasodilation (max: 26±3%, 21±4% and 28±7%, respectively), which was enhanced after endothelial denudation. In rats with transient MCA occlusion, a well‐known model of IS (90 min occlusion and 48 reperfusion) we observed a significantly reduced dilation to TNF, MCP‐1 and CINC‐1 in the ipsilateral MCA, whereas constriction of contralateral MCA was seen in response to TNF and CINC‐1. We also found reduced dilations of both ipsilateral and contralateral MCA in response to bradykinin and serotonin, but not to the NO‐donor, sodium nitroprusside in IS rats. Thus, TNF, MCP‐1 and CINC‐1 elicit endothelium‐independent vasodilation in MCA, which is significantly reduced after IS. Our data suggest reduced dilator or even enhanced constrictor signaling from damaged endothelium and indicate important role for these cytokines in regulating cerebral perfusion after IS. Grant Funding Source : Supported by NIH HL104126