Abstract

The failure of neuroprotective treatment-related clinical trials may be partially caused by unestablished animal models. Existing animal models are less likely to provide occlusion confined to the middle cerebral artery (MCA), making transarterial intervention difficult. We aimed to develop a novel focal stroke model using a microcatheter and zirconium dioxide that is non-magnetic under fluoroscopic guidance, which can monitor MCA occlusion and can improve hemorrhagic complications. Using male Sprague Dawley rats (n = 10), a microcatheter was navigated from the caudal ventral artery to the left internal carotid artery using an X-ray fluoroscopy to establish local occlusion. All rat cerebral angiographies were successful. No rats had hemorrhagic complications. Eight (80%) rats underwent occlusion of the MCA bifurcation by zirconium dioxide. Accidentally, the left posterior cerebral artery was failure embolized in 2 rats (20%). The median operating time was 8 min. All rats of occlusion MCA revealed an incomplete hemiparesis on the right side with neurological deficit score ranging from 1 to 3 (median 1, interquartile range 1–3) at 24 h after the induction of ischemia. Moreover, 2% 2,3,5-triphenyl tetrazolium chloride staining showed that the median infarct volume (mm3) was 280 (interquartile range 267–333) 24 h after the left MCA bifurcation occlusion. We present a novel rat model for focal stroke using a microcatheter and zirconium dioxide which does not affect the MRI. The model is predictable which is well confined within the territory supplied by the MCA, and reproducibility of this model is 80%. Fluoroscopy was able to identify which the MCA occlusion and model success while creating the model. It permitted exclusion of animals with complications from the experiment.

Highlights

  • The failure of neuroprotective treatment-related clinical trials may be partially caused by unestablished animal models

  • Eight (80%) rats underwent occlusion of the anterior cerebral artery (ACA)-middle cerebral artery (MCA) bifurcation by zirconia ball (Figs. 3B,C, 4B, Supplemental File—Video 1)

  • All MCAO rats revealed an incomplete hemiparesis on the right side with neurological deficit score ranging from 1 to 3 at 24 h after the induction of ischemia

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Summary

Introduction

The failure of neuroprotective treatment-related clinical trials may be partially caused by unestablished animal models. We aimed to develop a novel focal stroke model using a microcatheter and zirconium dioxide that is non-magnetic under fluoroscopic guidance, which can monitor MCA occlusion and can improve hemorrhagic complications. Fluoroscopy was able to identify which the MCA occlusion and model success while creating the model. It permitted exclusion of animals with complications from the experiment. Abbreviations ACA Anterior cerebral artery AchA Anterior choroidal artery CCA Common carotid artery ECA External carotid artery ICA Internal carotid artery IQR Interquartile range LAO Left anterior oblique MCA Middle cerebral artery MCAO Occlusion of the middle cerebral artery MRI Magnetic resonance imaging PCA Posterior cerebral artery

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