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通过小鼠颈总动脉修复实现再灌注的大脑中动脉闭塞

Middle Cerebral Artery Occlusion Allowing Reperfusion via Common Carotid Artery Repair in Mice.

作者信息

Trotman-Lucas Melissa, Kelly Michael E, Janus Justyna, Gibson Claire L

机构信息

Department of Neuroscience, Psychology and Behaviour, University of Leicester.

Preclinical Imaging Facility, Core Biotechnology Services, University of Leicester.

出版信息

J Vis Exp. 2019 Jan 23(143). doi: 10.3791/58191.

Abstract

The ischemic stroke is a major cause of adult long-term disability and death worldwide. The current treatments available are limited, with only tissue plasminogen activator (tPA) as an approved drug treatment to target ischemic strokes. Current research in the field of ischemic stroke focuses on better understanding the pathophysiology of stroke, to develop and investigate novel pharmaceutical targets. Reliable experimental stroke models are crucial for the progression of potential treatments. The middle cerebral artery occlusion (MCAO) model is clinically relevant and the most frequently used surgical model of ischemic stroke in rodents. However, the outcomes of this model, such as lesion volume, are associated with high levels of variability, particularly in mice. The alternative MCAO model described here allows the reperfusion of the common carotid artery (CCA) and the increased perfusion of the middle cerebral artery (MCA) territory, using a tissue pad with fibrinogen-based sealant to repair the vessel, and the improved welfare of the mice by avoiding external carotid artery (ECA) ligation. This reduces the reliance on the Circle of Willis, which is known to be highly anatomically variable in mice. Representative data show that using this alternative surgical approach decreases the variability in lesion volumes between the traditional MCAO approach and the alternative approach described here.

摘要

缺血性中风是全球成年人长期残疾和死亡的主要原因。目前可用的治疗方法有限,只有组织型纤溶酶原激活剂(tPA)作为批准用于治疗缺血性中风的药物。目前缺血性中风领域的研究重点是更好地理解中风的病理生理学,以开发和研究新的药物靶点。可靠的实验性中风模型对于潜在治疗方法的进展至关重要。大脑中动脉闭塞(MCAO)模型与临床相关,是啮齿动物中最常用的缺血性中风手术模型。然而,该模型的结果,如梗死体积,具有高度的变异性,特别是在小鼠中。这里描述的替代MCAO模型允许颈总动脉(CCA)再灌注,并增加大脑中动脉(MCA)区域的灌注,使用带有纤维蛋白原基密封剂的组织垫修复血管,并通过避免结扎颈外动脉(ECA)来改善小鼠的健康状况。这减少了对Willis环的依赖,已知Willis环在小鼠中的解剖结构差异很大。代表性数据表明,使用这种替代手术方法可降低传统MCAO方法与这里描述的替代方法之间梗死体积的变异性。

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