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Role of IL‐6 in a novel murine model of transient ischemic attack (853.1)
Author(s) -
Tang Ya Hui,
Vital Shanatel,
Granger D. Neil
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.853.1
Subject(s) - thrombus , medicine , stroke (engine) , thrombosis , cerebral infarction , platelet , bone marrow , cardiology , inflammation , ischemia , pathology , mechanical engineering , engineering
TIA is a precursor event in 7‐40% of patients who suffer from an ischemic stroke. This study involves the development of a murine model of TIA and explores the mechanism that accounts for the increased vulnerability of cerebral arterioles to thrombus development after TIA. TIA was simulated by brief (2.5 ‐ 10 min) occlusion of the middle cerebral artery. Thrombus formation in cerebral arterioles (induced by light/dye photoactivation of FITC‐dextran) was evaluated 1 ‐ 28 days after the TIA. Thrombosis was quantified using time of onset of platelet aggregation on the vessel wall and the time to complete flow cessation. While the brief period of TIA was not associated with neurological deficits or brain infarction (evaluated after 1 day), it yielded a pronounced and prolonged (up to 28 days) acceleration of thrombus formation, compared to control (sham) mice. Either immunoblockade of the interleukin‐6 (IL‐6) receptor or genetic deficiency of IL‐6, but not IL‐6‐/‐ bone marrow chimeras, signficantly protected against the TIA induced enhancement of thrombosis. Our findings indicate that the increased vulnerability of the cerebral vasculature to thrombus development after TIA can be recapitulated in a murine model, and that IL‐6, likely derived from brain tissue, rather than circulating immune cells, is an important mediator of, and possible therapeutic target for, TIA‐induced thrombogenesis. Grant Funding Source : HL26441