Kyng Kasper J, Skajaa Torjus, Kerrn-Jespersen Sigrid, Andreassen Christer S, Bennedsgaard Kristine, Henriksen Tine B
The Perinatal Research Unit, Department of Pediatrics, Institute of Clinical Medicine, Aarhus University Hospital;
The Perinatal Research Unit, Department of Pediatrics, Institute of Clinical Medicine, Aarhus University Hospital.
J Vis Exp. 2015 May 16(99):e52454. doi: 10.3791/52454.
Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world's 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials. Variations of the model have been applied in the study of adjunctive neuroprotective methods and piglet studies of xenon and melatonin have led to clinical phase I and II trials(1,2). The piglet HIE model is further used for neonatal resuscitation- and hemodynamic studies as well as in investigations of cerebral hypoxia on a cellular level. However, it is a technically challenging model and variations in the protocol may result in either too mild or too severe brain injury. In this article, we demonstrate the technical procedures necessary for establishing a stable piglet model of neonatal HIE. First, the newborn piglet (< 24 hr old, median weight 1500 g) is anesthetized, intubated, and monitored in a setup comparable to that found in a neonatal intensive care unit. Global hypoxia-ischemia is induced by lowering the inspiratory oxygen fraction to achieve global hypoxia, ischemia through hypotension and a flat trace amplitude integrated EEG (aEEG) indicative of cerebral hypoxia. Survival is promoted by adjusting oxygenation according to the aEEG response and blood pressure. Brain injury is quantified by histopathology and magnetic resonance imaging after 72 hr.
出生窒息可导致缺氧缺血性脑病（HIE），每年在全球造成66万例死亡，约占全球290万例新生儿死亡的四分之一。HIE的动物模型有助于理解HIE的病理生理学，并突出了围产期窒息导致脑损伤时发生的动态过程。因此，动物研究提出了损伤后治疗策略的时间窗。低温已在仔猪模型中作为HIE的治疗方法进行了测试，并随后在临床试验中被证明有效。该模型的变体已应用于辅助神经保护方法的研究，仔猪氙气和褪黑素研究已进入临床I期和II期试验（1,2）。仔猪HIE模型还进一步用于新生儿复苏和血流动力学研究以及细胞水平的脑缺氧研究。然而，它是一个技术上具有挑战性的模型，方案的变化可能导致脑损伤过轻或过重。在本文中，我们展示了建立稳定的新生仔猪HIE模型所需的技术程序。首先，将新生仔猪（<24小时龄，平均体重1500克）麻醉、插管，并在类似于新生儿重症监护病房的环境中进行监测。通过降低吸入氧分数诱导全身性缺氧缺血，以实现全身性缺氧、通过低血压导致的缺血以及脑电图（aEEG）平线幅度提示的脑缺氧。根据aEEG反应和血压调整氧合，以提高存活率。72小时后通过组织病理学和磁共振成像对脑损伤进行量化。
