A new model of focal cerebral ischemia in the miniature pig
A new model of focal cerebral ischemia in the miniature pig
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DOI：
10.3171/ped.2006.104.2.123
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发表时间：
2006-02-01
影响因子：
4.1
通讯作者：
Saito, N
中科院分区：
文献类型：
--
作者：
Imai, H;Konno, K;Saito, N
Object.这组研究的目的是设计一个微创的，可重复的脑回卒中模型。本文提供了有关小型猪灰质和白色物质缺血性损伤的手术技术和定量方法的信息。将16只雄性小型猪随机分为3组，并进行经颅手术，包括额颞入路眶缘截骨术，用于永久性大脑中动脉闭塞（MCAO; 5只动物）、永久性颈内动脉闭塞（ICAO; 6只动物）和假手术（5只动物）。组织学定位和磁共振（MR）成像用于描绘缺血性损伤的区域。在MCAO组、ICAO组和假手术组中，直接从MR图像测量的梗死体积分别为16.2 ± 1.1、1.5 ± 0.5和0.0 ± 0.0 cm（3）（平均值±标准差[SD]，p < 0.001）。通过组织学分析和MR成像确定的缺血区域显示出良好的相关性（r（2）= 0.86，p < 0.0001）。使用淀粉样前体蛋白（APP）抗体的免疫组织化学染色来评估轴突损伤并计算轴突损伤的APP总评分：MCAO为44.8 +/- 2.9，ICAO为13.2 +/- 6.6，假手术动物为0.0 +/- 0.0（平均值+/- SD，p < 0.002）。这种新的局灶性脑缺血模型在灰质和白色物质中诱导可再现量的缺血性损伤，并且对于脑回缺血的病理生理学的研究和在开始人体临床试验之前评估药物的治疗功效具有重要的实用性。
Object. The purpose of this set of studies is to design a minimally invasive, reproducible stroke model in the gyrencephalic brain. This paper provides information on both surgical technique and methods Of quantification of ischemic damage to both gray and white matter in the miniature pig.Methods. Sixteen male miniature pigs were randomly divided into three groups and underwent transcranial surgery involving a frontotemporal approach with orbital rim osteotomy For permanent middle cerebral artery occlusion (MCAO; five animals), permanent internal carotid artery occlusion (ICAO; six animals), and a sham operation (five animals). Histological mapping and magnetic resonance (MR) imaging were used to delineate the areas of: ischemic damage. The volumes of infarction measured directly from MR images were 16.2 +/- 1.1 1.5 +/- 0.5, and 0.0 +/- 0.0 cm(3) (mean +/- standard deviation [SD], p < 0.001) in the MCAO, ICAO, and sham-operated groups, respectively. The areas of ischemia identified through histological analysis and MR imaging showed a good correlation (r(2) = 0.86, p < 0.0001). Immunohistochemical staining with an amyloid precursor protein (APP) antibody was used to evaluate axonal damage and calculate a total APP score for axonal damage of 44.8 +/- 2.9 in the MCAO, 13.2 +/- 6.6 in the ICAO, and 0.0 +/- 0.0 (mean +/- SD, p < 0.002) in the sham-operated animals.Conclusions. This new model of focal cerebral ischemia induces a reproducible amount of ischemic damage in both gray and white matter, and has significant utility for studies of the pathophysiology of ischemia in the gyrencephalic brain and for assessment of the therapeutic efficacy of drugs prior to the initiation of human clinical trials.