Roohey T, Raju T N, Moustogiannis A N
Department of Pediatrics, University of Illinois, Chicago 60612, USA.
Early Hum Dev. 1997 Jan 20;47(2):115-46. doi: 10.1016/s0378-3782(96)01773-2.
We critically evaluated various design features from 292 animal studies related to perinatal hypoxic-ischemic encephalopathy (HIE). Rodents were the most frequently used animals in HIE research (26%), followed by piglets (23%) and sheep (22%). Asphyxia with or without ischemia was the most predominant method of producing experimental brain damage, but there were significant variations in specific details, particularly regarding the method and duration of brain insult. In 71% (207/292) of studies the CNS outcomes were tested within 24 h of experimental insult and in 29% (85/292) they were tested 24 h or more after the insult. Acute CNS metabolic end-points were assessed in 82-100% of all studies. In 90% of studies the chronological age of the animal was equivalent to that of human term newborn infant. However, in only 23% (67/292) were clinical neurological, developmental or behavioral outcomes evaluated, and in only 26% (76/292) was neuropathology assessed. While no single animal model was found to be ideal for all HIE research, some models were distinctly superior to others, depending upon the specific research question. The fetal sheep, newborn lamb and piglet models are well suited for the study of acute and subacute metabolic and physiologic endpoints, whereas the rodent and primate models could be used for long-term neurological and behavioral outcome experiments as well. We also feel that standardizing the study design features, including an HI insult method that produces consistent and predictable brain damage is urgently needed. Studies in neuro-ethology should explore how well brains of various animals compare with that of the newborn human infant. There is also a need for developing animal models that mimic clinical entities in which long-term neuro-developmental and behavioral outcomes can be assessed.
我们严格评估了292项与围产期缺氧缺血性脑病（HIE）相关的动物研究的各种设计特征。啮齿动物是HIE研究中最常用的动物（26%），其次是仔猪（23%）和绵羊（22%）。伴有或不伴有缺血的窒息是造成实验性脑损伤的最主要方法，但具体细节存在显著差异，尤其是在脑损伤的方法和持续时间方面。在71%（207/292）的研究中，中枢神经系统结局在实验性损伤后24小时内进行测试，在29%（85/292）的研究中，在损伤后24小时或更长时间进行测试。在所有研究的82%-100%中评估了急性中枢神经系统代谢终点。在90%的研究中，动物的实际年龄与足月新生儿相当。然而，只有23%（67/292）的研究评估了临床神经学、发育或行为结局，只有26%（76/292）的研究评估了神经病理学。虽然没有发现单一的动物模型对所有HIE研究都是理想的，但根据具体的研究问题，一些模型明显优于其他模型。胎羊、新生羔羊和仔猪模型非常适合研究急性和亚急性代谢及生理终点，而啮齿动物和灵长类动物模型也可用于长期神经学和行为结局实验。我们还认为，迫切需要规范研究设计特征，包括采用能产生一致且可预测脑损伤的缺氧缺血性损伤方法。神经行为学研究应探索各种动物的大脑与新生儿大脑的相似程度。还需要开发能够模拟临床实体的动物模型，以便评估长期神经发育和行为结局。
