Delayed thrombosis after traumatic brain injury in rats
Delayed thrombosis after traumatic brain injury in rats
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DOI：
10.1089/neu.2004.21.1756
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发表时间：
2004-12-01
影响因子：
4.2
通讯作者：
Chopp, M
中科院分区：
文献类型：
--
作者：
Lu, DY;Mahmood, A;Chopp, M
继发性血栓形成可导致创伤性脑损伤（TBI）引起的脑缺血。在这项研究中，我们试图研究血管内血栓形成的时间和空间分布，并评估阿托伐他汀（一种β-羟基-β-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂）对TBI后血栓形成的影响。对体重350-400 g的年轻雄性Wistar大鼠进行控制性皮质撞击损伤，并分别在TBI后1和4 h以及1、3、8和15 d处死（5只大鼠/时间点）。为了评价阿托伐他汀对血管内血栓形成的作用，对大鼠进行TBI，随后从TBI后1天开始口服施用阿托伐他汀（1 mg/kg），然后每天一次，直到在TBI后3、8和15天处死（5只大鼠/时间点）。在处死动物之前，抽取血液并使用酶联免疫吸附测定（ELISA）用于测量von Willibrand因子和血小板活性。制备脑组织用于组织学分析。数据显示：（1）迟发性血栓形成出现在病灶边缘区和海马CA 3区，开始于伤后1-4 h，1-3 d达到高峰，8 d和15 d后逐渐下降;（2）血管内血栓形成也出现在皮层、纹状体和胼胝体的其他区域，但呈分散分布;（3）迟发性血栓由血小板、纤维蛋白和vWF组成;（4）阿托伐他汀降低血浆vWF水平和血小板活性可减少TBI后迟发性血栓形成。这些数据表明，阿托伐他汀减少血管内血栓形成归因于TBI引起的止血障碍。
Secondary thrombosis may contribute to cerebral ischemia caused by traumatic brain injury (TBI). In this study, we sought to investigate the temporal and spatial profiles of intravascular thrombosis and to evaluate the effect of atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor, on thrombosis after TBI. Young male Wistar rats weighing 350-400 g were subjected to controlled cortical impact injury, and were sacrificed at 1 and 4 h, and 1, 3, 8, and 15 days after TBI (5 rats/time point), respectively. For the evaluation of the effects of atorvastatin on intravascular thrombosis, rats were subjected to TBI, and subsequently atorvastatin (1 mg/kg) was orally administered starting 1 day after TBI and then daily until sacrifice at 3, 8, and 15 days after TBI (5 rats/time point). Before sacrifice of animals, blood was withdrawn and employed for the measurement of von Willibrand factor and platelet activity using enzyme-linked immunoabsorbant assay (ELISA). Brain tissues were prepared for histological analysis. The data show that (1) delayed thrombosis is present in the lesion boundary zone and in the hippocampal CA3 region, starting at 1-4 h, peaking at 1-3 days, and then declining at 8 and 15 days after TBI; (2) intravascular thrombosis also occurs in the other areas of cortex, striatum, and corpus callosum, but with a scattered distribution; (3) delayed thrombi are composed of platelets, fibrin, and vWF; and (4) reduction of the plasma vWF level and platelet activity by atorvastatin decreases delayed thrombosis after TBI. These data suggest that atorvastatin reduces intravascular thrombosis attributed to hemostatic disturbances caused by TBI.