Malignant infarction of the middle cerebral artery in a porcine model. A pilot study.
Malignant infarction of the middle cerebral artery in a porcine model. A pilot study.
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DOI：
10.1371/journal.pone.0172637
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Sahuquillo J
中科院分区：
文献类型：
--
作者：
Arikan F;Martínez-Valverde T;Sánchez-Guerrero Á;Campos M;Esteves M;Gandara D;Torné R;Castro L;Dalmau A;Tibau J;Sahuquillo J
来自啮齿动物研究的物种间变异性和糟糕的临床翻译表明，迫切需要大型脑回动物卒中模型。我们提出了一项原理验证研究，描述了一种常见的猪大脑中动脉恶性梗塞(MCA)的替代动物模型，并说明了它的一些潜在应用。我们报道了代谢模式，离子分布，脑氧分压(PtiO2)，磺脲受体1(SUR1)的表达，以及瞬时受体潜力Melastatin 4(TRPM4)。5头2.5~3月龄雌性杂交猪(大白猪×长白猪)经额颞侧入路进行5小时大脑中动脉缺血区脑梗塞。术中监测核心区和半影区，以确定代谢和离子分布。用2，3，5-三苯基四氮唑氯化铵染色和免疫组织化学方法检测SUR1和TRPM4的表达。PtiO2监测显示，大脑中动脉阻塞后，核心区的PtiO2值突然下降到接近0毫米汞柱。每小时脑微透析显示梗塞组织葡萄糖(0.03 mM)和丙酮酸(0.003 mM)浓度降低，乳酸(8.87 mM)、乳酸/丙酮酸比值(4202)、甘油(588μM)和钾浓度(27.9 mmoL/L)升高。免疫组织化学分析显示SUR1-TRPM4通道表达增加。本研究的目的是通过经颅阻断普通猪的大脑中动脉，建立一种可替代同脑动物的大动物恶性大脑中动脉梗塞模型的可行性。该模型可用于脑缺血机制的详细研究和神经保护策略的开发。
Interspecies variability and poor clinical translation from rodent studies indicate that large gyrencephalic animal stroke models are urgently needed. We present a proof-of-principle study describing an alternative animal model of malignant infarction of the middle cerebral artery (MCA) in the common pig and illustrate some of its potential applications. We report on metabolic patterns, ionic profile, brain partial pressure of oxygen (PtiO2), expression of sulfonylurea receptor 1 (SUR1), and the transient receptor potential melastatin 4 (TRPM4). A 5-hour ischemic infarct of the MCA territory was performed in 5 2.5-to-3-month-old female hybrid pigs (Large White x Landrace) using a frontotemporal approach. The core and penumbra areas were intraoperatively monitored to determine the metabolic and ionic profiles. To determine the infarct volume, 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry analysis was performed to determine SUR1 and TRPM4 expression. PtiO2 monitoring showed an abrupt reduction in values close to 0 mmHg after MCA occlusion in the core area. Hourly cerebral microdialysis showed that the infarcted tissue was characterized by reduced concentrations of glucose (0.03 mM) and pyruvate (0.003 mM) and increases in lactate levels (8.87mM), lactate-pyruvate ratio (4202), glycerol levels (588 μM), and potassium concentration (27.9 mmol/L). Immunohistochemical analysis showed increased expression of SUR1-TRPM4 channels. The aim of the present proof-of-principle study was to document the feasibility of a large animal model of malignant MCA infarction by performing transcranial occlusion of the MCA in the common pig, as an alternative to lisencephalic animals. This model may be useful for detailed studies of cerebral ischemia mechanisms and the development of neuroprotective strategies.