中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (23): 2087-2094.doi: 10.4103/1673-5374.147936

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

腔内技术建立更恒定的恒河猴缺血性脑卒中模型

  

  • 收稿日期:2014-11-22 出版日期:2014-12-10 发布日期:2014-12-10
  • 基金资助:

    973 项目(2011CB707804)

A more consistent intraluminal rhesus monkey model of ischemic stroke

Bo Zhao 1, Guowei Shang 1, Jian Chen 1, Xiaokun Geng 1, Xin Ye 2, Guoxun Xu 2, Ju Wang 3, Jiasheng Zheng 4, Hongjun Li 4, Fauzia Akbary 5, Shengli Li 3, Jing Lu 3, Feng Ling 1, Xunming Ji 1, 6   

  1. 1 Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
    2 Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China
    3 Department of Laboratory Animal Science, Capital Medical University, Beijing, China
    4 Radiology Department, Beijing Youan Hospital, Capital Medical University, Beijing, China
    5 Wayne State University School of Medicine, Detroit, MI, USA
    6 Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
  • Received:2014-11-22 Online:2014-12-10 Published:2014-12-10
  • Contact: Xunming Ji, Department of Neurology, Xuanwu Hospital, Capital Medical University, Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China 100053, Beijing, China, jixm@ccmu.edu.cn.
  • Supported by:

    This study was financially supported by grants from the National Key Basic Research Program (973 Program) of China, No. 2011CB707804; Beijing Municipal Science and Technology Project, No. 2121100005312016.

摘要:

血管内技术的颅脑创伤性较少,更接近于临床卒中患者的病理生理,但似乎有更高的变异性,限制了实验评估的准确性。因此,我们将8只成年健康恒河猴随机分为大脑中动脉起始段梗死组(M1)和大脑中动脉M2段梗死组,每组4只,采用选择性神经介入放射技术,行大脑中动脉弹簧圈(1 mm × 10 cm)栓塞2 h,建立脑缺血模型,回收弹簧圈后恢复血流再通。通过苏木精-伊红染色、数字减影血管造影、磁共振血管造影、磁共振成像和神经功能评分检测后发现。8只恒河猴均栓塞成功,24 h后脑组织出现明确的相应供血区脑组织缺血,并出现相应神经功能缺失。与大脑中动脉起始段(M1)梗死组相比,大脑中动脉M2段梗死组梗死体积较小,神经功能恢复较好。结果证实,利用血管内弹簧圈栓塞技术,可使恒河猴出现恒定的可逆性大脑中动脉闭塞。大脑中动脉M2段梗死的恒河猴缺血性脑卒中模型梗死体积和神经损伤更小更恒定,可应用于脑损伤修复领域的研究。

关键词: 神经再生, 脑损伤, 恒河猴, 模型, 大脑中动脉, 微弹簧圈, 脑梗塞, 脑卒中, 介入治疗, DSA, 磁共振成像, 神经影像学

Abstract:

Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research.

Key words: nerve regeneration, brain injury, rhesus monkeys, model middle cerebral artery, microcoil, infarction, stroke, interventional therapy, digital subtraction angiography, magnetic resonance image, neuroimaging, neuroregeneration