Embolic middle cerebral artery occlusion model using thrombin and fibrinogen composed clots in rat.

Embolic middle cerebral artery occlusion model using thrombin and fibrinogen composed clots in rat.
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DOI:
10.1016/j.jneumeth.2012.09.006
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发表时间:
2012-11-15
影响因子:
3
通讯作者:
Yang, Shao-Hua
Yang, Shao-Hua
中科院分区:
医学4区
文献类型:
--
作者:
Ren, Ming;Lin, Zi-Jing;Qian, Hai;Choudhury, Gourav Roy;Liu, Ran;Liu, Hanli;Yang, Shao-Hua

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缺血性卒中占人类卒中总数的80%以上,主要累及大脑中动脉(MCA)区域。将同种异体血栓注入颈内动脉和大脑中动脉建立的栓塞性卒中模型非常接近于人类卒中,并已被广泛用于卒中研究。研究表明,血栓的大小和组成对卒中模型的重复性至关重要。在本研究中,我们通过添加凝血酶和纤维蛋白原来修饰同种凝块的形成,从而产生分布均匀的纤维蛋白,并与红细胞紧密交联。我们使用不同大小的混合血栓对大鼠大脑中动脉闭塞模型进行了优化。在用PE-60导管制作的1 mm长的混合性血栓的栓塞性大脑中动脉闭塞模型中,血栓精确地堆积在大脑中动脉分叉处,并在大脑中动脉区域出现高度重复性的缺血病变。我们进一步测试了重组组织型纤溶酶原激活剂(RtPA)在大脑中动脉闭塞模型中的作用。与对照组相比,在栓塞后1小时给予rTPA可诱导血栓溶解,改善神经预后,并显著减少缺血损伤体积。综上所述,我们利用同种异体血液、凝血酶和纤维蛋白原制成的血栓建立了一种可重复性的大脑中动脉闭塞模型。混合凝块可精确定位于大脑中动脉分叉处,对rtPA的溶栓治疗有反应。
Ischemic stroke accounts for over 80% in total human stroke which mostly affect middle cerebral artery (MCA) territory. Embolic stroke models induced by injection of homologous clots into the internal carotid artery and MCA closely mimic human stroke and have been commonly used in stroke research. Studies indicate that the size and composition of clots are critical for the reproducibility of the stroke model. In the present study, we modified the homologous clots formation by addition of thrombin and fibrinogen which produced even distribution of fibrin with tight cross linkage of red blood cells. We optimized the embolic MCA occlusion model in rats using different size of the mixed clots. A precise lodgment of the clots at the MCA bifurcation and highly reproducible ischemic lesion in the MCA territory were demonstrated in the embolic MCA occlusion model induced by injection of 10 pieces of 1-mm long mixed clots made in PE-60 catheter. We further tested the effect of recombinant tissue plasminogen activator (rtPA) in this embolic MCA occlusion model. rtPA induced thrombolysis, improved neurological outcome, and significantly reduced ischemic lesion volume when administered at 1 hour after embolism as compared with control. In summary, we have established a reproducible embolic MCA occlusion model using clots made of homologous blood, thrombin and fibrinogen. The mixed clots enable precise lodgment at the MCA bifurcation which is responsive to thrombolytic therapy of rtPA.
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