ELR-CXC chemokine antagonism is neuroprotective in a rat model of ischemic stroke

被引:20
作者
Connell, Barry J. [1 ]
Gordon, John R. [2 ]
Saleh, Tarek M. [1 ]
机构
[1] Univ Prince Edward Isl, Atlantic Vet Coll, Dept Biomed Sci, Charlottetown, PE C1A 4P3, Canada
[2] Univ Saskatchewan, Dept Med, Div Respirol Crit Care & Sleep Med, Saskatoon, SK S7N 0W0, Canada
关键词
Anti-inflammatory; Neutrophil; Stroke; Reperfusion injury; Middle cerebral artery occlusion; CEREBRAL-ARTERY OCCLUSION; INTESTINAL ISCHEMIA; REPERFUSION INJURY; LUNG INJURY; INFLAMMATORY RESPONSES; RECEPTORS CXCR1; BRAIN; PREVENTION; REPERTAXIN; INHIBITOR;
D O I
10.1016/j.neulet.2015.08.041
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Inflammation-related cerebral damage mediated by infiltrating neutrophils following reperfusion plays a role in reperfusion-induced brain damage subsequent to a stroke event. The ELR-CXC family of chemokines are CXCR1 and CXCR2 agonists that are known to drive neutrophil migration and activation. The present study demonstrated the benefit of anti-inflammatory therapy in the treatment of ischemic stroke with the administration of the competitive ELR-CXC chemokine antagonist, CXCL8((3-72))K11R/G31P (G31P). Male Sprague-Dawley rats were anaesthetized, and the middle cerebral artery (MCA) was occluded for 30 min followed by 5.5 h of reperfusion. Pretreatment with G31P resulted in a significant, dose-dependent (approximately 61-72%) decrease in infarct volumes compared to vehicle-treated animals, but neuroprotection was also observed when G31P (0.5 mg/kg) was administered 1 or 3 h following the start of reperfusion. The neuroprotection observed following the administration of this competitive CXCR1/CXCR2 antagonist may present therapeutic opportunities for addressing reperfusion-induced inflammatory damage in patients presenting with transient ischemic episodes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:117 / 122
页数:6
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