Yager Jerome Y, Ashwal Stephen
Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada.
Pediatr Neurol. 2009 Mar;40(3):156-67. doi: 10.1016/j.pediatrneurol.2008.10.025.
Animal models are often presumably the first step in determining mechanisms underlying disease, and the approach and effectiveness of therapeutic interventions. Perinatal brain damage, however, evolves over months of gestation, during the rapid maturation of the fetal and newborn brain. Despite marked advances in our understanding of these processes and technologic advances providing an improved window on the timing and duration of injury, neonatal brain injury remains a "moving target" regarding our ability to "mimic" its processes in an animal model. Moreover, interfering with normal processes of development as part of a therapeutic intervention may do "more harm than good." Hence, controversy continues over which animal model can reflect human disease states. Numerous models have provided information regarding the pathophysiology of brain damage in term and preterm infants. Our challenges consist of identifying infants at greatest risk for permanent injury, identifying the timing of injury, and adapting therapies that provide more benefit than harm. A combination of appropriately suitable animal models to conduct these studies will bring us closer to understanding human perinatal damage and the means to treat it.
动物模型通常被认为是确定疾病潜在机制以及治疗干预方法和效果的第一步。然而，围产期脑损伤是在胎儿和新生儿大脑快速成熟的数月妊娠期内逐渐发展的。尽管我们对这些过程的理解有了显著进展，并且技术进步为损伤的时间和持续时间提供了更好的观察窗口，但就我们在动物模型中“模拟”其过程的能力而言，新生儿脑损伤仍然是一个“移动靶标”。此外，作为治疗干预的一部分干扰正常发育过程可能“弊大于利”。因此，关于哪种动物模型能够反映人类疾病状态的争议仍在继续。众多模型已经提供了有关足月儿和早产儿脑损伤病理生理学的信息。我们面临的挑战包括识别永久性损伤风险最高的婴儿、确定损伤时间，以及采用利大于弊的治疗方法。结合适当合适的动物模型来进行这些研究将使我们更接近了解人类围产期损伤及其治疗方法。
