Using animal models to improve care of neonatal encephalopathy.
Using animal models to improve care of neonatal encephalopathy.
复制标题
使用动物模型改善新生儿脑病的护理。
DOI：
10.1136/archdischild-2015-309927
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Lingam I
中科院分区：
文献类型：
--
作者：
Lingam I
新生儿脑病（NE）是世界范围内造成残疾和死亡的重大负担。1利用动物模型研究围产期缺氧缺血（HI）已有200多年的历史，最初研究表明早产动物比足月动物更能耐受窒息，而足月动物又比成年动物更能抵抗窒息。20世纪50年代至70年代，对灵长类动物模型的研究表明，脑损伤的模式明显受到HI的严重程度和类型的影响;这些研究导致了两种损伤模式的描述，即急性完全窒息和慢性部分窒息。5在过去的30年里，通过使用NE动物模型来了解HI后脑损伤的时间和演变取得了进展。在人类婴儿中观察到磷-31（31 P）磁共振波谱（MRS）的脑能量代谢在出生后短暂恢复，尽管有重症监护支持，但在出生后的数小时和数天内下降，由此触发，7项新生仔猪8和大鼠9的研究允许比人类胎儿和新生儿更精确地研究HI后事件的病理生理学和时间。建立这种“二次”能量故障的时间导致了这样一个概念，即存在一个机会窗口，在主要损伤后开始干预可以改变脑损伤的轨迹。从床边到实验室的想法和问题的转变将治疗性低温从研究假设转变为标准临床护理6（图1）。优化治疗性低温之外的新生儿神经保护需要进一步的临床前研究，在使用适当的动物模型时要仔细考虑，以确保研究结果的有效性，安全性和可翻译性。
Neonatal encephalopathy (NE) is responsible for a significant burden of disability and death worldwide. 1 The use of animal models in the study of perinatal hypoxia-ischaemia (HI) has a history of over 200years; studies initially showed that the premature animal is more tolerant of asphyxia than a term animal, which is in turn more resistant to asphyxia than an adult. 2 3 In the 1950s to the 1970s, studies in the primate model showed that the pattern of brain injury was clearly influenced by the severity and type of HI; these studies led to a description of two patterns of injury, namely acute total asphyxia 4 and chronic partial asphyxia. 5 In the last 30years, progress was made by using animal models of NE to understand the timing and evolution of brain injury after HI. Triggered by the observation in human babies that brain energy metabolism on phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) transiently recovered after birth and declined in the subsequent hours and days after birth despite intensive care support, 7 studies in the newborn piglet 8 and rat 9 allowed pathophysiology and timing of events after HI to be studied more precisely than in the human fetus and neonate. Establishing the timing of this ‘secondary’energy failure led to the concept that a window of opportunity existed whereby an intervention started after the primary insult could alter the trajectory of brain damage. The translation of the ideas and questions from bedside to bench moved therapeutic hypothermia from a research hypothesis to standard clinical care 6 (figure 1). Optimising neonatal neuroprotection beyond therapeutic hypothermia requires further preclinical research with careful thought in using appropriate animal models to ensure efficacy, safety and translatability of the findings.