Characterization of a novel thrombotic middle cerebral artery occlusion model in monkeys that exhibits progressive hypoperfusion and robust cortical infarction

Characterization of a novel thrombotic middle cerebral artery occlusion model in monkeys that exhibits progressive hypoperfusion and robust cortical infarction
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DOI:
10.1016/j.jneumeth.2005.01.019
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发表时间:
2005-07-15
影响因子:
3
通讯作者:
Matsuoka, N
Matsuoka, N
中科院分区:
医学4区
文献类型:
--
作者:
Maeda, M;Takamatsu, H;Matsuoka, N

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为了建立食蟹猴血栓性大脑中动脉(MCA)闭塞模型,我们测定了MCA主干和大脑皮质的血流量、脑损伤和神经功能缺损,并与机械性MCA闭塞模型进行了比较。虎红处理后,通过在MCA上施加绿色光以光化学方式诱导血栓闭塞;通过MCA夹闭3小时诱导机械闭塞。在血栓模型中,MCA主干的通畅性表现为两种模式:永久性闭塞或周期性血流减少(CFR)。在夹闭模型中,局部脑血流量(rCBF)在闭塞期间减少,随后是缺血后过度灌注,而在血栓闭塞模型中,rCBF减少呈时间依赖性扩大。血栓闭塞模型的脑梗死和神经功能评分显著大于夹闭模型。在组织学评估中,在血栓性但非夹闭闭塞后的皮质中观察到含有髓过氧化物酶和纤维蛋白原阳性细胞的微血栓。这些结果共同表明,这种血栓性MCA闭塞模型,因为它显示脑微循环障碍,可以提供一个重要的平台,了解进行性缺血,以及评估潜在的治疗药物。(c)2005 Elsevier B. V.保留所有权利。
In an attempt to establish a thrombotic middle cerebral artery (MCA) occlusion model using cynomolgus monkeys, we measured the blood flow in the main MCA tract and cerebral cortex, brain damage, and neurological deficits, and compared them with those of mechanical MCA occlusion model. Thrombotic occlusion was induced photochemically by green light application on the MCA following rose bengal treatment; mechanical occlusion was induced by MCA clipping for 3 h. Patency of the main MCA tract showed two patterns in the thrombotic model: permanent occlusion or cyclical flow reduction (CFR). Regional cerebral blood flow (rCBF) decreased during occlusion followed by post-ischemic hyperperfusion in the clipping model, whereas rCBF reduction expanded time-dependently in the thrombotic occlusion model. Brain infarction and neurological scores in the thrombotic occlusion model were significantly larger than those in the clipping occlusion model. In histological assessment, microthrombi containing myeloperoxidase- and fibrinogen-positive cells were observed in the cortex following the thrombotic but not clipping occlusion. These results collectively suggest that this thrombotic MCA occlusion model, because it shows impairment of cerebral microcirculation, could provide a vital platform for understanding progressive ischemia as well as for evaluating potential therapeutic drugs. (c) 2005 Elsevier B.V. All rights reserved.