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.

Highlights

  • A major cause of cerebral stroke is focal ischemia in the territory of the middle cerebral artery

  • We describe an alternative murine surgical procedure where external carotid artery (ECA) ligation is avoided and the common carotid artery (CCA) incision is repaired, permitting reperfusion through the CCA, independent of the Circle of Willis (CoW)

  • We demonstrate how to undertake middle cerebral artery occlusion (MCAO) through CCA vessel filament insertion followed by CCA vessel repair, which involves a tissue pad and sealant application to permit reperfusion

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Summary

Introduction

A major cause of cerebral stroke is focal ischemia in the territory of the middle cerebral artery. Www.jove.com rats to result in a successful reperfusion through the CCA15 We have applied this approach successfully in mice[11] and report here the protocol which results in a reduced variability in lesion volume, the main outcome measure used in experimental stroke studies. In this protocol, we demonstrate how to undertake MCAO through CCA vessel filament insertion followed by CCA vessel repair, which involves a tissue pad and sealant application to permit reperfusion. All experiments are reported in accordance with the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines[16]

Preparation
Middle Cerebral Artery Occlusion Surgery
Post-occlusion
Post-operative Care
Magnetic Resonance Imaging and Image Processing
Representative Results
Discussion
Full Text
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