Painter M J
Division of Child Neurology, Children's Hospital of Pittsburgh, PA 15213, USA.
Semin Pediatr Neurol. 1995 Mar;2(1):37-56. doi: 10.1016/s1071-9091(05)80004-x.
Animal models have contributed immensely to our understanding of hypoxic ischemic encephalopathy in the newborn. A number of animal models have been used, including both primate and subprimate species. Although the Rhesus monkey model has a dramatically similar pathological distribution of brain injury when compared with the human, other pathologic processes secondary to asphyxia may be more appropriately assessed in other species. The maxim that because primates are closer on the phylogenetic tree to humans than are subprimates all observations in the primate are applicable to the human is simply not true. Understanding of the neurochemical consequences of asphyxia in the past decade have arisen from experiments primarily in the neonatal rat. We have come to understand that not only is the hypoxic event of major significance, but that, once reperfused, reoxygenation causes further injury. Free-radical generation following reperfusion may be massive and may further contribute to cell membrane injury. These observations have lead to rational theoretic approaches to the treatment of hypoxic ischemic brain injury. On the other hand, previously used treatments such as osmotic agents and glucocorticoids would appear to be not only inefficacious but hazardous in the treatment of hypoxic ischemic brain injury. The role of nitric oxide (NO) in the pathogenesis of brain injury is yet uncertain, but there is little doubt that it plays a significant role. Although survival of the immature animal subjected to hypoxic environment is longer than in the mature animal, the central nervous system of the immature animal is more sensitive to glutamate and N-Methyl-D-aspartate (NMDA) receptor-mediated injury.
动物模型对我们理解新生儿缺氧缺血性脑病有极大帮助。已经使用了多种动物模型，包括灵长类和非灵长类物种。尽管恒河猴模型与人类相比脑损伤的病理分布极为相似，但窒息继发的其他病理过程在其他物种中可能更适合评估。那种认为因为灵长类在系统发育树上比非灵长类更接近人类，所以在灵长类中的所有观察结果都适用于人类的观点根本不正确。过去十年中对窒息神经化学后果的认识主要来自新生大鼠的实验。我们已经明白，不仅缺氧事件至关重要，而且一旦再灌注，复氧会导致进一步损伤。再灌注后自由基的产生可能大量增加，并可能进一步导致细胞膜损伤。这些观察结果促使人们对缺氧缺血性脑损伤的治疗采取合理的理论方法。另一方面，以前使用的治疗方法，如渗透剂和糖皮质激素，在治疗缺氧缺血性脑损伤时似乎不仅无效而且有害。一氧化氮（NO）在脑损伤发病机制中的作用尚不确定，但毫无疑问它起着重要作用。尽管处于缺氧环境中的未成熟动物的存活时间比成熟动物长，但未成熟动物的中枢神经系统对谷氨酸和N-甲基-D-天冬氨酸（NMDA）受体介导的损伤更敏感。
