Zhang Z, Zhang R L, Jiang Q, Raman S B, Cantwell L, Chopp M
Department of Neurology, Henry Ford Health Science Center, Detroit, Michigan, USA.
J Cereb Blood Flow Metab. 1997 Feb;17(2):123-35. doi: 10.1097/00004647-199702000-00001.
We developed a fibrin-rich thrombotic focal cerebral ischemic model with reproducible and predictable infarct volume in rats. In male Wistar rats (n = 77), a thrombus was induced at the origin of the middle cerebral artery (MCA) by injection of thrombin via an intraluminal catheter placed in the intracranial segment of the internal carotid artery (ICA). Thrombus induction and consequent ischemic cell damage were examined by histopathological analysis and neurological deficit scoring, and by measuring changes in cerebral blood flow (CBF) using laser-Doppler flowmetery (LDF), perfusion-weighted imaging (PWI), and by diffusion weighted imaging (DWI). Histopathology revealed that a fibrin-rich thrombus localized to the origin of the right MCA. Regional cerebral blood flow (rCBF) in the right parietal cortex was reduced by 34-58% of preinjection levels after injection of thrombin in rats administered 30 U of thrombin (n = 10). Magnetic resonance imaging (MRI) showed a reduction in CBF and a hyperintensity DWI encompassing the territory supplied by the right MCA. The infarct volume in rats administered 80 U of thrombin was 31.29 +/- 12.9% of the contralateral hemisphere at 24 h (n = 13), and 34.7 +/- 16.4% of the contralateral hemisphere at 168 h (n = 6). Rats administered 30 U of thrombin exhibited a hemispheric infarct volume of 34.0 +/- 14.5% (n = 9) at 24 h and 29.7 +/- 13.9% (n = 8) at 168 h. In addition, thrombotic rats (n = 3) treated with recombinant tissue plasminogen activator (rt-PA) (10 mg/kg) 2 h after thrombosis showed that CBF rapidly returned towards preischemic values as measured by PWI. This model of thrombotic ischemia is relevant to thromboembolic stroke in humans and may be useful in documenting the safety and efficacy of thrombolytic intervention as well as for investigating therapies complementary to antithrombotic therapy.
我们建立了一种富含纤维蛋白的血栓性局灶性脑缺血模型，该模型在大鼠中具有可重复且可预测的梗死体积。在雄性Wistar大鼠（n = 77）中，通过经放置在颈内动脉（ICA）颅内段的腔内导管注射凝血酶，在大脑中动脉（MCA）起始处诱导形成血栓。通过组织病理学分析和神经功能缺损评分，以及使用激光多普勒血流仪（LDF）、灌注加权成像（PWI）和扩散加权成像（DWI）测量脑血流量（CBF）的变化，来检查血栓形成及随之而来的缺血性细胞损伤。组织病理学显示，富含纤维蛋白的血栓位于右侧MCA起始处。在注射30 U凝血酶的大鼠（n = 10）中，注射凝血酶后右侧顶叶皮质的局部脑血流量（rCBF）降至注射前水平的34 - 58%。磁共振成像（MRI）显示CBF降低，且右侧MCA供血区域出现弥散加权成像（DWI）高信号。注射80 U凝血酶的大鼠在24小时时梗死体积为对侧半球的31.29±12.9%（n = 13），在168小时时为对侧半球的34.7±16.4%（n = 6）。注射30 U凝血酶的大鼠在24小时时半球梗死体积为34.0±14.5%（n = 9），在168小时时为29.7±13.9%（n = 8）。此外，血栓形成后2小时用重组组织型纤溶酶原激活剂（rt-PA）（10 mg/kg）治疗的血栓形成大鼠（n = 3）显示，通过PWI测量，CBF迅速恢复至缺血前值。这种血栓性缺血模型与人类的血栓栓塞性中风相关，可能有助于记录溶栓干预的安全性和有效性，以及研究抗血栓治疗的补充疗法。
