Systemic neutrophil activation in a mouse model of ischemic stroke and reperfusion.

Systemic neutrophil activation in a mouse model of ischemic stroke and reperfusion.
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DOI:
10.1177/1099800410384500
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发表时间:
2011-04
影响因子:
2.5
通讯作者:
Ritter L
Ritter L
中科院分区:
医学4区
文献类型:
--
作者:
Morrison H;McKee D;Ritter L

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作为对损伤和疾病的自然反应,中性粒细胞被激活,粘附在微血管上,迁移到脑组织中,并释放出活性氧和蛋白酶等有毒物质。这种中性粒细胞反应发生在缺血性中风后血流返回脑组织(再灌注)时。因此,激活的全身中性粒细胞的存在增加了缺血性卒中后再灌注期间组织损伤的可能性。尽管大鼠模型实验表明,活化的中性粒细胞在脑缺血再灌注损伤中起关键作用,但在小鼠模型中,缺血性卒中后再灌注时全身中性粒细胞活化的情况知之甚少。本研究的目的是表征小鼠缺血性卒中模型再灌注后15分钟和24小时的全身白细胞反应和中性粒细胞CD11b表达。对雄性C57Bl/6小鼠进行了短暂性大脑中动脉闭塞再灌注(tMCAO)或假手术的腔内细丝法。测定自动白细胞计数和人工白细胞(WBC)差异计数。流式细胞术检测全身中性粒细胞表面CD11b表达。数据表明,系统性中性粒细胞激活的损伤潜力早在15分钟开始,并在再灌注开始后24小时保持明显。此外,由于在C57Bl/6背景下培育的转基因小鼠模型越来越多地用于阐明缺血性卒中后再灌注损伤的单一机制,本研究的发现为未来研究在该背景品系下转基因小鼠模型中缺血性卒中后再灌注中性粒细胞反应的损伤潜力奠定了基础。
As a natural response to injury and disease, neutrophils activate, adhere to the microvasculature, migrate into brain tissue, and release toxic substances such as reactive oxygen species and proteases. This neutrophil response occurs when blood flow is returned to brain tissue (reperfusion) after ischemic stroke. Thus, the presence of activated systemic neutrophils increases the potential for tissue injury during reperfusion after ischemic stroke. Although experiments in rat models suggest that activated neutrophils play a pivotal role in cerebral ischemia reperfusion injury, little is known about systemic neutrophil activation during reperfusion following ischemic stroke in a mouse model. The purpose of this study was to characterize systemic leukocyte responses and neutrophil CD11b expression 15-min and 24-hr post-reperfusion in a mouse model of ischemic stroke. The intraluminal filament method of transient middle cerebral artery occlusion (tMCAO) with reperfusion or a sham procedure was performed in male C57Bl/6 mice. Automated leukocyte counts and manual white blood cell (WBC) differential counts were measured. Flow cytometry was used to assess systemic neutrophil surface CD11b expression. The data suggest that the damaging potential of systemic neutrophil activation begins as early as 15 min and remains evident at 24 hr after the initiation of reperfusion. In addition, because transgenic mouse models, bred on a C57Bl/6 background, are increasingly used to elucidate single mechanisms of reperfusion injury after ischemic stroke, findings from this study are foundational for future investigations examining the damaging potential of neutrophil responses post-reperfusion after ischemic stroke in genetically altered mouse models within this background strain.
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