A novel mouse model of thromboembolic stroke.
A novel mouse model of thromboembolic stroke.
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DOI：
10.1016/j.jneumeth.2015.09.013
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发表时间：
2015-12-30
影响因子：
3
通讯作者：
Alkayed NJ
中科院分区：
文献类型：
--
作者：
Chen Y;Zhu W;Zhang W;Libal N;Murphy SJ;Offner H;Alkayed NJ
我们先前在野生型(WT)小鼠和表达人类白细胞抗原DR2(DR2-TG)的转基因小鼠中证明了组织型纤溶酶原激活剂(TPA)可以减少机械性大脑中动脉闭塞(MCAO)后的脑梗塞范围。临床上，tPA通过溶解阻塞大脑动脉血流的血栓来限制缺血性损伤。为了模拟临床情况，我们建立了一种新的血栓栓塞性卒中小鼠模型，并在WT和DR2-TG小鼠上测试了tPA的疗效。将自体血液抽到PE-8导管中，导管内充满2IU的α-凝血酶。在短暂地将导管暴露在空气中后，导管被重新插入外部动脉(ECA)，并前进到颈内动脉(ICA)，以便在MCA分叉处进行血管内凝血酶注射。为了验证该模型，我们测试了tPA对WT和DR2-TG小鼠大脑中动脉区域激光多普勒血流灌注(LDP)和脑梗塞面积的影响。该程序导致LDP持续下降，并导致高度可重复性的缺血性损害。当在血栓形成后15分钟给予tPA时，在血栓形成后24小时，在WT和DR2-TG中，tPA使LDP恢复，并导致梗塞面积显著缩小。我们的模型显著减少了手术时间，需要一次麻醉暴露，并产生一致和可预测的梗塞，变异性和死亡率低。在一种新的血管内血栓栓塞性卒中小鼠模型中，我们验证了tPA在恢复血流和减少梗塞方面的有效性。
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. Autologous blood is withdrawn into a PE-8 catheter filled with 2 IU α-thrombin.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. 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. Our model significantly reduces surgery time, requires a single anesthesia exposure, and produces a consistent and predictable infarction, with low variability and mortality. We validated the efficacy of tPA in restoring blood flow and reducing infarct in a new model of endovascular thromboembolic stroke in the mouse.