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Direct arterial damage and neurovascular unit disruption by mechanical thrombectomy in a rat stroke model.

大鼠卒中模型中机械取栓的直接动脉损伤和神经血管单元破坏。

  • 影响因子:3.44
  • DOI:10.1002/jnr.24671
  • 作者列表:"Sasaki R","Yamashita T","Tadokoro K","Matsumoto N","Nomura E","Omote Y","Takemoto M","Hishikawa N","Ohta Y","Abe K
  • 发表时间:2020-06-18
Abstract

:Mechanical thrombectomy (MT) is a standard treatment for acute ischemic stroke that could cause hemorrhagic complications. We aimed to evaluate the pathology of MT-induced arterial damage and neurovascular unit (NVU) disruption in relation to tissue-type plasminogen activator (tPA) injection for acute ischemic stroke. We induced transient middle cerebral artery occlusion in male SHR/Izm rats for 2 hr. This was followed by reperfusion with/without tPA (3 mg/kg) and "rough suture" insertion that mimicked MT once or thrice (MT1 or MT3). Compared with the control group, the tPA + MT3 group presented with an increase in the cerebral infarct and hemorrhage with severer IgG leakage. Moreover, structural damage reaching the tunica media was detected in the MT3 and tPA + MT3 groups. The tPA + MT3 group presented with increased matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression with some MMP9-positive cells expressing a neutrophil marker myeloperoxidase. Furthermore, basal lamina detachment from astrocyte foot processes was observed in the tPA + MT1 and tPA + MT3 groups. These findings suggest that MT causes direct arterial damage, as well as VEGF and MMP9 upregulation, which results in NVU disruption and hemorrhagic complications in acute ischemic stroke, especially when combined with tPA.

摘要

机械血栓切除术 (MT) 是急性缺血性卒中的标准治疗方法,可引起出血性并发症。我们旨在评价 MT 诱导的动脉损伤和神经血管单元 (NVU) 破坏与组织型纤溶酶原激活剂 (tPA) 注射治疗急性缺血性卒中的病理学关系。我们诱导雄性 SHR/Izm 大鼠短暂性大脑中动脉闭塞 2 h。随后使用/不使用 tPA (3 mg/kg) 和模拟 MT 一次或三次 (MT1 或 MT3) 的 “粗线” 插入进行再灌注。与对照组相比,tPA + MT3 组脑梗死和出血增多,IgG 渗漏加重。此外,在 MT3 和 tPA + MT3 组中检测到到达被膜介质的结构损伤。TPA + MT3 组出现基质 metalloproteinase-9 (MMP-9) 和血管内皮生长因子 (VEGF) 表达增加,部分 MMP9-positive 细胞表达中性粒细胞标记物髓过氧化物酶。此外,在 tPA + MT1 和 tPA + MT3 组中观察到星形胶质细胞足突的基底椎板脱离。这些发现表明 MT 引起直接动脉损伤,以及 VEGF 和 MMP9 上调,导致急性缺血性卒中的 NVU 破坏和出血并发症,尤其是与 tPA 联合使用时。

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作者列表:["Thilarajah S","Bower KJ","Hao PY","Tan D","Williams G","Larik A","Wai BC","Koh G","Clark RA"]

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影响因子:2.57
发表时间:2020-01-06
DOI:10.1007/s12031-019-01474-x
作者列表:["Cheng, Xiao","Yang, Ying-Lin","Li, Wei-Han","Liu, Man","Zhang, Shan-Shan","Wang, Yue-Hua","Du, Guan-Hua"]

METHODS:Cerebral ischemia-reperfusion (I/R) is characterized by initial transient cerebral ischemia followed by reperfusion. Various pathophysiological processes are involved in brain injury and functional recovery during cerebral I/R. There are few studies on dynamic metabolic process after cerebral I/R. The present study was to observe dynamic alteration of brain injury, functional recovery, and metabolites after cerebral I/R in rats and discover potential metabolic markers. The cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 90 min, following reperfusion in rats. The results of cerebral infarction area, cerebral edema, and behavior test showed that there were dynamic changes in brain injury and functional recovery at different periods after cerebral I/R. Further analysis showed that the brain injury was severe on the first day of cerebral I/R, and there was a significant functional recovery from the 7th day of cerebral I/R, followed by an aggravation trend of brain injury from the days 7 to 28. Furthermore, Matrix-assisted laser desorption ionization mass spectrometry imaging analysis showed that the expression of ATP, glucose, and citric acid on 7th day was the highest during cerebral I/R, which indicated that energy metabolism and oxidative phosphorylation played important roles during cerebral I/R. In addition, the untargeted metabolomic results showed that the level of isocitric acid, the ratio of oxyglutaric acid/glutamic acid, and the level of pyruvic acid associated with the TCA cycle were also the highest on the 7th day during cerebral I/R, which indicated that the transient spontaneous recovery of ischemic brain on the 7th day after ischemia-reperfusion might be related to oxidative phosphorylation and energy metabolism in the brain in this period. In conclusion, the results suggest that some small molecule metabolites participate in the brain injury and functional recovery during cerebral I/R, which is of great significance to the development of therapeutic drugs and diagnostic markers.

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影响因子:2.75
发表时间:2020-01-01
DOI:10.1007/s00702-019-02124-7
作者列表:["Wang, Xiaodong","Shi, Cunxian","Pan, Hongxia","Meng, Xiaowen","Ji, Fuhai"]

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