- 作者：F. Montecucco ; R. da Silva ; R.A. Fraga-Silva ; L. Capettini ; S. Quintao ; S. Lenglet ; G. Pelli ; K. Galan ; V. Braunersreuther ; K. Schaller ; A.E. Proudfoot ; N. Stergiopulos ; R.A. Santos ; Y. Gasche ; F. Mach ; J.-C. Copin
- 刊名：Cytokine
- 出版年：2012
- 出版时间：September, 2012
- 年：2012
- 卷：59
- 期：3
- 页码：517-518
- 全文大小：140 K
Introduction
The presence and rupture of a carotid plaque inducing a severe arterial lumen stenosis have been associated with a consequent acute ischemic stroke in the brain. Treatment with chemokine-binding proteins isolated from tick salivary glands (also called ¡°Evasins¡±) has been shown to reduce leukocyte recruitment in animal models of several diseases, such as acute myocardial infarction and rheumatoid arthritis. In the present study, we investigated the potential benefits of the selective inhibition of neutrophil recruitment (mediated by Evasin-3 treatment) in both primary and secondary prevention of ischemic stroke.Methods
Two mouse models of shear stress-induced carotid atherosclerosis and cerebral ischemia and reperfusion were used (for ischemic stroke primary and secondary prevention strategies, respectively). In the first model, preventive chronic treatment with Evasin-3 (5 daily injections [at 1 microg/mouse] per week for total 3-week treatment period) was tested as compared with control vehicle (PBS) in ApoE?/? mice submitted to the implantation of ¡°cast¡± carotid device. In the second model, C57Bl/6 mice aged from 8 to 12 weeks were used. The left middle cerebral artery (MCA) was occluded for 45 min with an intraluminal Dafilon 6.0 nylon suture. Then, blood flow was re-established and mice were followed up for 24 h of reperfusion. Five minutes after MCA occlusion, mice received one intraperitoneal injection of Evasin-3 (10 microg/mouse) or control vehicle (PBS). Leukocyte infiltration, infarct size and blood brain barrier (BBB) permeability were determined at 24 h of reperfusion.
Results
In atherosclerotic plaques of ApoE?/? mice, primary prevention treatment with Evasin-3 was associated with the reduction of neutrophils and MMP-9 content in aortic root and carotid plaques as compared to control vehicle. Secondary prevention treatment approach (after ischemic stroke) with Evasin-3 was associated with a significant reduction in neutrophil infiltration in the ischemic brain as compared to control vehicle. However, this anti-inflammatory effect was not associated with any improvements in cerebral infarct size, edema and BBB permeability.
Conclusion
Primary prevention strategy of Evasin-3 treatment reduced atherosclerotic plaque vulnerability for ischemic stroke. Acute Evasin-3 administration after cerebral ischemia onset significantly reduced brain inflammation, but failed to improve post-stroke outcomes.
References
None.