Thrombotic Stroke in the Anesthetized Monkey (Macaca mulatta): Characterization by MRI - A Pilot Study
Thrombotic Stroke in the Anesthetized Monkey (Macaca mulatta): Characterization by MRI - A Pilot Study
复制标题
DOI：
10.1159/000335309
复制
发表时间：
2012-01-01
影响因子：
2.9
通讯作者：
Orset, Cyrille
中科院分区：
文献类型：
--
作者：
Gauberti, Maxime;Obiang, Pauline;Orset, Cyrille
背景：在大型非人灵长类动物中缺乏相关的脑卒中模型阻碍了这种脑血管疾病的创新诊断/治疗方法的发展。我们的目标是在麻醉的猴子中开发一种新的和临床相关的栓塞性中风模型，该模型结合了现成的临床成像技术，并允许药物输送包括再灌注策略的可能性。方法：在麻醉（七氟醚）雄性恒河猴（Macaca mulatta）大脑中动脉（MCA）腔内注射凝血酶。序贯MRI检查（包括血管造影、FLAIR、PWI、DWI和钆增强T1W成像）在3T临床MRI中进行。在整个调查过程中监测生理生化参数。结果：手术程序一旦标准化，所有手术动物的大脑中动脉都会发生短暂性闭塞。所有实验动物均表现为自发性再灌注，发生时间在离体后2小时至7天。80%的研究动物出现扩散/灌注不匹配。24小时的缺血性病变不影响MCA的浅表和深部区域。部分动物在出血后7天出现出血性转化。结论：在这项研究中，我们在麻醉的非人灵长类动物中建立了一个临床前相关的栓塞性中风模型。巴塞尔S. Karger股份有限公司版权所有
Background: The lack of a relevant stroke model in large nonhuman primates hinders the development of innovative diagnostic/therapeutic approaches concerned with this cerebrovascular disease. Our objective was to develop a novel and clinically relevant model of embolic stroke in the anesthetized monkey that incorporates readily available clinical imaging techniques and that would allow the possibility of drug delivery including strategies of reperfusion. Methods: Thrombin was injected into the lumen of the middle cerebral artery (MCA) in 12 anesthetized (sevoflurane) male rhesus macaques (Macaca mulatta). Sequential MRI studies (including angiography, FLAIR, PWI, DWI, and gadolinium-enhanced T1W imaging) were performed in a 3T clinical MRI. Physiological and biochemical parameters were monitored throughout the investigations. Results: Once standardized, the surgical procedure induced transient occlusion of the middle cerebral artery in all operated animals. All animals studied showed spontaneous reperfusion, which occurred some time between 2 h and 7 days post-ictus. Eighty percent of the studied animals showed diffusion/perfusion mismatch. The ischemic lesions at 24 h spared both superficial and profound territories of the MCA. Some animals presented hemorrhagic transformation at 7 days post-ictus. Conclusion: In this study, we developed a pre-clinically relevant model of embolic stroke in the anesthetized nonhuman primate. Copyright (C) 2012 S. Karger AG, Basel