Maeda Masashi, Takamatsu Hiroyuki, Furuichi Yasuhisa, Noda Akihiko, Awaga Yuji, Tatsumi Mitsuyoshi, Yamamoto Masashi, Ichise Rikiya, Nishimura Shintaro, Matsuoka Nobuya
Department of Neuroscience, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., 2-1-6 Kashima, Yodogawa-Ku, Osaka 532-8514, Japan.
J Neurosci Methods. 2005 Jul 15;146(1):106-15. doi: 10.1016/j.jneumeth.2005.01.019. Epub 2005 Feb 24.
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 3h. 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.
为了尝试使用食蟹猴建立血栓性大脑中动脉（MCA）闭塞模型，我们测量了大脑中动脉主要分支和大脑皮质的血流、脑损伤及神经功能缺损，并将其与机械性MCA闭塞模型进行比较。在孟加拉玫瑰红处理后，通过对MCA照射绿光以光化学诱导血栓形成闭塞；通过夹闭MCA 3小时诱导机械性闭塞。在血栓形成模型中，大脑中动脉主要分支的通畅情况呈现两种模式：永久性闭塞或周期性血流减少（CFR）。在夹闭模型中，闭塞期间局部脑血流（rCBF）减少，随后出现缺血后灌注，而在血栓形成闭塞模型中，rCBF减少呈时间依赖性扩展。血栓形成闭塞模型中的脑梗死和神经功能评分显著高于夹闭闭塞模型。在组织学评估中，血栓形成闭塞后在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，而夹闭闭塞后未观察到。这些结果共同表明，这种血栓性MCA闭塞模型由于显示出脑微循环受损，可为理解进行性缺血以及评估潜在治疗药物提供重要平台。
