A Stable Focal Cerebral Ischemia Injury Model in Adult Mice: Assessment Using 7T MR Imaging

Zhang, Fujun; Guo, Ruomi; Yang, Ming‐Hua; Wen, Xianlong; Shen, Jun

doi:10.3174/ajnr.a2887

Cited by 19 publications

(15 citation statements)

References 27 publications

(33 reference statements)

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“…Despite the fact the hippocampus, thalamus and amygdala are not supplied by the MCA, it is not uncommon for these regions to show evidence of ischemic injury following MCAO [ 19 , 44 , 45 , 59 ], for several reasons. First and foremost, C57BL/6 mice may be more susceptible to variation in intraluminal filament MCAO compared to other strains owing to a common lack of patency in posterior communicating arteries (PComA) [ 31 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice

et al. 2016

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The intraluminal filament model of middle cerebral artery occlusion (MCAO) in mice and rats has been plagued by inconsistency, owing in part to the multitude of variables requiring control. In this study we investigated the impact of several major variables on survival rate, lesion volume, neurological scores, cerebral blood flow (CBF) and body weight including filament width, time after reperfusion, occlusion time and the choice of surgical method. Using the Koizumi method, we found ischemic injury can be detected as early as 30 min after reperfusion, to a degree that is not statistically different from 24 h post-perfusion, using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We also found a distinct increase in total lesion volume with increasing occlusion time, with 30–45 min a critical time for the development of large, reproducible lesions. Furthermore, although we found no significant difference in total lesion volume generated by the Koizumi and Longa methods of MCAO, nor were survival rates appreciably different between the two at 4 h after reperfusion, the Longa method produces significantly greater reperfusion. Finally, we found no statistical evidence to support the exclusion of data from animals experiencing a CBF reduction of <70% in the MCA territory following MCAO, using laser-Doppler flowmetry. Instead we suggest the main usefulness of laser-Doppler flowmetry is for guiding filament placement and the identification of subarachnoid haemorrhages and premature reperfusion. In summary, this study provides detailed evaluation of the Koizumi method of intraluminal filament MCAO in mice and a direct comparison to the Longa method.

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Section: Discussionmentioning

confidence: 99%

A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice

et al. 2016

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“…Eighty-seven [1]percent of all strokes in humans are ischemic and most frequently caused by cerebral thromboembolism [2–4]. Cerebral thrombosis or embolism leads to ischemic stroke with cerebral thrombosis being more common [5, 6]. Cerebral thrombosis is the formation of a blood clot at a congested cerebral vessel due to atherosclerosis of brain arteries, normally caused by an accumulation of fatty deposits inside the blood vessels.…”

Section: Introductionmentioning

confidence: 99%

Partial MHC Constructs Treat Thromboembolic Ischemic Stroke Characterized by Early Immune Expansion

Dotson

Chen

Zhu

et al. 2015

Transl. Stroke Res.

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Inflammation and thrombosis are tightly linked, with inflammation contributing to thromboembolism and to stroke outcome. Thromboembolism is a frequent cause of ischemic stroke, yet the most used occlusion mouse models of experimental stroke do not effectively replicate thromboembolism. Our group recently described a novel thromboembolic mouse model of stroke that successfully occludes the middle cerebral artery with high reproducibility. In the current study, we characterize the peripheral and local immune outcomes as well as the ischemic response to immune therapy in a clinically relevant mouse model of thromboembolic stroke. Brain and spleen tissues were harvested 24 hours after thromboembolic stroke and cells immunophenotyped by flow cytometry. We observed a significant increase in neutrophils and early activated T cells in the spleen and an increase in neutrophils and activated monocytes/microglia in the ischemic cortex after thromboembolic stroke. Moreover, as was shown previously for transient MCAO models, treatment of thromboembolic stroke with partial MHC constructs significantly reduced ischemic damage indicating an equivalent effect of this immune-based therapy in the thromboembolic model that better mimics the pathophysiology of human stroke.

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“…The CV of infarct volume in rodent experimental stroke models has a wide range between 0.05 to 2, depending on the model, choice of anesthetic and how well physiological and hemodynamic variables are controlled, among other factors (Liu et al, 2009). Similarly, Zhang F et al found that infarct location and size were highly variable in mouse stroke models, with the thromboembolic model showing highest variability in infarct size of 0.44 and lowest 7-day survival (Zhang et al, 2012). …”

Section: Discussionmentioning

confidence: 96%

A novel mouse model of thromboembolic stroke

Chen

Zhu

Zhang

et al. 2015

Journal of Neuroscience Methods

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Background We previously demonstrated that tissue plasminogen activator (tPA) reduces infarct size after mechanical middle cerebral artery occlusion (MCAO) in wild-type (WT) mice and transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). Clinically, tPA limits ischemic damage by dissolving the clot blocking blood flow through a cerebral artery. To mimic the clinical situation, we developed a new mouse model of thromboembolic stroke, and tested the efficacy of tPA in WT and DR2-Tg mice. New Method Autologous blood is withdrawn into a PE-8 catheter filled with 2 IU α-thrombin. After exposing the catheter briefly to air, the catheter is reintroduced into the external (ECA) and advanced into the internal carotid artery (ICA) to allow for intravascular injection of thrombin at the MCA bifurcation. To validate the model, we tested the effect of tPA on laser-Doppler perfusion (LDP) over the MCA territory and infarct size in WT and DR2-Tg mice. Results The procedure results in a consistent drop in LDP, and leads to a highly reproducible ischemic lesion. When administered at 15 min after thrombosis, tPA restored LDP and resulted in a significant reduction in infarct size at 24 hours after thrombosis in both WT and DR2-Tg. Comparison with Existing Methods Our model significantly reduces surgery time, requires a single anesthesia exposure, and produces a consistent and predictable infarction, with low variability and mortality. Conclusion We validated the efficacy of tPA in restoring blood flow and reducing infarct in a new model of endovascular thromboembolic stroke in the mouse.

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A Stable Focal Cerebral Ischemia Injury Model in Adult Mice: Assessment Using 7T MR Imaging

Abstract: BACKGROUND AND PURPOSE:A stable stroke experimental model is highly desirable for performing longitudinal studies using MR imaging. The purpose of this study is to establish a stable focal cerebral ischemia model with a high survival rate in adult mice.

Cited by 19 publications

References 27 publications

A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice

A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice

Partial MHC Constructs Treat Thromboembolic Ischemic Stroke Characterized by Early Immune Expansion

A novel mouse model of thromboembolic stroke

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