Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
J Neurosci Res. 2020 Oct;98(10):2018-2026. doi: 10.1002/jnr.24671. Epub 2020 Jun 18.
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.
机械血栓切除术（MT）是治疗急性缺血性中风的标准方法，但可能会导致出血性并发症。我们旨在评估与组织型纤溶酶原激活剂（tPA）注射治疗急性缺血性中风相关的 MT 引起的动脉损伤和神经血管单元（NVU）破坏的病理学。我们在雄性 SHR/Izm 大鼠中诱导短暂性大脑中动脉闭塞 2 小时。然后进行再灌注，同时给予或不给予 tPA（3mg/kg）和“粗糙缝线”插入，模拟 MT 一次或三次（MT1 或 MT3）。与对照组相比，tPA+MT3 组的脑梗死和出血增加，IgG 渗漏更严重。此外，在 MT3 和 tPA+MT3 组中检测到达到中膜的结构损伤。tPA+MT3 组的基质金属蛋白酶-9（MMP-9）和血管内皮生长因子（VEGF）表达增加，一些 MMP9 阳性细胞表达中性粒细胞标志物髓过氧化物酶。此外，在 tPA+MT1 和 tPA+MT3 组中观察到基底膜从星形胶质细胞足突分离。这些发现表明 MT 会导致直接的动脉损伤，以及 VEGF 和 MMP9 的上调，从而导致急性缺血性中风中的 NVU 破坏和出血性并发症，尤其是与 tPA 联合使用时。
