Imai Hideaki, Konno Kenjiro, Nakamura Mitsunobu, Shimizu Tatsuya, Kubota Chisato, Seki Koji, Honda Fumiaki, Tomizawa Shinichiro, Tanaka Yukitaka, Hata Hidekazu, Saito Nobuhito
Department of Neurosurgery, Institute of Experimental Animal Research, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
J Neurosurg. 2006 Feb;104(2 Suppl):123-32. doi: 10.3171/ped.2006.104.2.123.
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.
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 cm3 (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 (r2 = 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.
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.
本系列研究的目的是在脑回脑构建一种微创、可重复的中风模型。本文提供了小型猪脑缺血性损伤的手术技术及灰质和白质损伤定量方法的相关信息。
16只雄性小型猪随机分为三组，接受经颅手术，采用额颞入路并眶缘截骨术以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）以及假手术（5只动物）。组织学绘图和磁共振（MR）成像用于描绘缺血损伤区域。分别从MR图像直接测量的梗死体积在MCAO组、ICAO组和假手术组中为16.2±1.1、1.5±0.5和0.0±0.0 cm³（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（r² = 0.86，p<0.0001）。使用淀粉样前体蛋白（APP）抗体进行免疫组织化学染色以评估轴突损伤，并计算轴突损伤的总APP评分为：MCAO组44.8±2.9，ICAO组13.2±6.6，假手术动物组为0.0±0.0（均值±SD，p<0.002）。
这种新型局灶性脑缺血模型在灰质和白质中均可诱导出可重复的缺血性损伤量，对于脑回脑缺血病理生理学研究以及在人类临床试验启动前评估药物治疗效果具有重要作用。
