A reproducible Endothelin-1 model of forelimb motor cortex stroke in the mouse
A reproducible Endothelin-1 model of forelimb motor cortex stroke in the mouse
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DOI：
10.1016/j.jneumeth.2014.05.014
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发表时间：
2014-08-15
影响因子：
3
通讯作者：
Vanderluit, Jacqueline L.
中科院分区：
文献类型：
--
作者：
Roome, R. Brian;Bartlett, Robert F.;Vanderluit, Jacqueline L.
背景资料：尽管有许多转基因小鼠品系可用于研究单个基因在促进中风后神经修复中的作用，但很少有研究利用这种技术，主要是由于缺乏可重现的小鼠缺血性损伤模型。皮质内注射内皮素-1（ET-1）是一种有效的血管收缩剂，可可靠地导致大鼠局灶性梗死伴行为缺陷。相比之下，ET 1梗死在小鼠中显着较小，不产生一致的行为defictions.New方法：我们已经修改了ET 1缺血模型，以针对前前肢运动皮层（aFMC），并表明这产生了可重复的局灶性缺血性损伤小鼠一致的行为缺陷。此外，我们已经开发了一种新的分析，通过量化爪拖动behaviors.Results：ET 1注射损伤深层神经元的aFMC产生可重复的赤字上的楼梯测试的圆柱测试。圆柱体测试分析表明，注射后没有前肢不对称，但是，我们观察到一种新的爪子拖动行为的小鼠，这是一个积极的迹象，损害的FMC.Comparison与现有的方法：以前的ET 1研究已经证明了不一致的行为缺陷，但是，有针对性的ET 1注射到aFMC可靠的结果在楼梯赤字。我们表明，在缸测试中的爪拖动行为的分析是一个更敏感的措施，比经典的前肢不对称analysis.Conclusions损害的FMC：我们已经开发了一个局灶性缺血性损伤小鼠模型，结果在可重复的行为缺陷，并可用于测试未来的再生疗法。(C)2014爱思唯尔有限公司版权所有。
Background: Despite the availability of numerous transgenic mouse lines to study the role of individual genes in promoting neural repair following stroke, few studies have availed of this technology, primarily due to the lack of a reproducible ischemic injury model in the mouse. Intracortical injections of Endothelin-1 (ET1) a potent vasoconstrictive agent, reliably produces focal infarcts with concomitant behavioral deficits in rats. In contrast, ET1 infarcts in mice are significantly smaller and do not generate consistent behavioral deficits.New method: We have modified the ET1 ischemia model to target the anterior forelimb motor cortex (aFMC) and show that this generates a reproducible focal ischemic injury in mice with consistent behavioral deficits. Furthermore, we have developed a novel analysis of the cylinder test by quantifying paw-dragging behavior.Results: ET1 injections which damage deep layer neurons in the aFMC generate reproducible deficits on the staircase test. Cylinder test analysis showed no forelimb asymmetry post-injection; however, we observed a novel paw-dragging behavior in mice which is a positive sign of damage to the FMC.Comparison with existing methods: Previous ET1 studies have demonstrated inconsistent behavioral deficits; however, targeting ET1 injections to the aFMC reliably results in staircase deficits. We show that analysis of paw-dragging behavior in the cylinder test is a more sensitive measure of damage to the FMC than the classical forelimb asymmetry analysis.Conclusions: We have developed a focal ischemic injury model in the mouse that results in reproducible behavioral deficits and can be used to test future regenerative therapies. (C) 2014 Elsevier B.V. All rights reserved.