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Distal Occlusion of the Middle Cerebral Artery in Mice: Are We Ready to Assess Long-Term Functional Outcome?

机译:小鼠大脑中动脉远端闭塞:我们准备好评估长期功能结果了吗?

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摘要

Rodent animal models of stroke are widely used with brain ischemia inducible by various occlusion methods. Permanent or transient occlusion of the distal portion of the middle cerebral artery (MCAO) offers a reproducible model with low mortality rates, and it is the most likely model of choice for mid- and long-term studies to assess neurorepair or long-term effects of neuroprotective drugs. Therefore, a measurable and stable neurological assessment would be required to evaluate sensorimotor and cognitive deficits at short and long terms as suggested by the Stroke Therapy Academic Industry Roundtable preclinical recommendations. We review the usefulness of different tests used to measure functional outcome after distal MCAO in mice and further sustain these data with our own multilaboratories’ experience. Results show that several tests were suitable to detect neurological deterioration at short term. Grip strength and latency to move have shown some usefulness at long term, with important differences between strains, while less clear are the data for the corner test. Important strain differences in terms of infarct volume are also reported in this study. Statistical power analysis and sample size calculation of our data confirmed the value of grip strength and latency to move tests but suggest that larger sample size would be required. In conclusion, there are no robust data supporting the use of a specific behavior test to assess long-term functional outcome after distal MCAO in mice. This is an important limitation since translational basic research should provide data to help further clinical trial evaluation. New multicenter studies with larger sample size and specific mouse strains are needed to confirm the validity of tests, such as the corner, latency to move or grip strength.
机译:中风的啮齿动物模型广泛用于通过各种闭塞方法诱导的脑缺血。大脑中动脉远端(MCAO)的永久性或短暂性闭塞提供了可重现的模型,死亡率低,它是评估神经修复或长期作用的中长期研究的最可能选择的模型神经保护药。因此,如中风疗法学术行业圆桌会议的临床前建议所建议的那样,就需要短期和长期评估感觉运动和认知功能障碍的测量和稳定的神经系统评估。我们回顾了用于测量小鼠远端MCAO后功能结局的各种测试的有用性,并借助我们自己的多实验室经验进一步保留了这些数据。结果表明,几种测试适合短期内检测神经系统恶化。从长远来看,握力和移动潜伏期已显示出一定的用处,各菌株之间存在重要差异,而拐角试验的数据尚不清楚。在该研究中还报告了在梗塞体积方面重要的应变差异。统计功效分析和数据样本量计算证实了握力强度和移动测试潜伏期的价值,但建议需要更大的样本量。总之,没有可靠的数据支持使用特定的行为测试来评估小鼠远端MCAO后的长期功能结局。这是一个重要的限制,因为翻译基础研究应提供数据以帮助进一步的临床试验评估。需要新的具有更大样本量和特定小鼠品系的多中心研究来确认测试的有效性,例如转角,移动潜伏期或握力强度。

著录项

  • 来源
    《Translational Stroke Research》 |2013年第3期|297-307|共11页
  • 作者单位

    Neurovascular Research Laboratory and Neurology Department Vall d’Hebron Research Institute Universitat Autònoma de Barcelona">(1);

    Serine Proteases and Pathophysiology of the Neurovascular Unit GIP CYCERON INSERM UMR-S U919 University Caen Basse-Normandie">(2);

    Institute of Experimental and Clinical Pharmacology and Toxicology University of Lübeck">(3);

    Neurovascular Research Laboratory and Neurology Department Vall d’Hebron Research Institute Universitat Autònoma de Barcelona">(1);

    Serine Proteases and Pathophysiology of the Neurovascular Unit GIP CYCERON INSERM UMR-S U919 University Caen Basse-Normandie">(2);

    Department of Neurobiology AI Virtanen Institute for Molecular Sciences University of Eastern Finland">(4);

    Neuroprotection Research Laboratory Department of Neurology and Radiology Massachusetts General Hospital Neuroscience Program Harvard Medical School">(5);

    Serine Proteases and Pathophysiology of the Neurovascular Unit GIP CYCERON INSERM UMR-S U919 University Caen Basse-Normandie">(2);

    Institute of Experimental and Clinical Pharmacology and Toxicology University of Lübeck">(3);

    Neurovascular Research Laboratory and Neurology Department Vall d’Hebron Research Institute Universitat Autònoma de Barcelona">(1);

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Ischemia; Mouse; Distal MCAO; Functional outcome;

    机译:缺血;老鼠;远端MCAO;功能结果;

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