Department of Neurology, Harvard Medical School, Boston, Massachusetts; Department of Pediatric Newborn Medicine, Harvard Medical School, Boston, Massachusetts.
Pediatr Neurol. 2019 Jun;95:42-66. doi: 10.1016/j.pediatrneurol.2019.02.016. Epub 2019 Feb 27.
Prematurity, especially preterm birth (less than 32 weeks' gestation), is common and associated with high rates of both survival and neurodevelopmental disability, especially apparent in cognitive spheres. The neuropathological substrate of this disability is now recognized to be related to a variety of dysmaturational disturbances of the brain. These disturbances follow initial brain injury, particularly cerebral white matter injury, and involve many of the extraordinary array of developmental events active in cerebral white and gray matter structures during the premature period. This review delineates these developmental events and the dysmaturational disturbances that occur in premature infants. The cellular mechanisms involved in the genesis of the dysmaturation are emphasized, with particular focus on the preoligodendrocyte. A central role for the diffusely distributed activated microglia and reactive astrocytes in the dysmaturation is now apparent. As these dysmaturational cellular mechanisms appear to occur over a relatively long time window, interventions to prevent or ameliorate the dysmaturation, that is, neurorestorative interventions, seem possible. Such interventions include pharmacologic agents, especially erythropoietin, and particular attention has also been paid to such nutritional factors as quality and source of milk, breastfeeding, polyunsaturated fatty acids, iron, and zinc. Recent studies also suggest a potent role for interventions directed at various experiential factors in the neonatal period and infancy, i.e., provision of optimal auditory and visual exposures, minimization of pain and stress, and a variety of other means of environmental behavioral enrichment, in enhancing brain development.
早产，特别是极早产（妊娠 32 周以下）很常见，并且与高存活率和神经发育障碍相关，尤其是在认知领域。目前认为这种残疾的神经病理学基础与大脑各种不成熟的发育障碍有关。这些障碍继发于初始脑损伤，特别是脑白质损伤，并涉及早产儿脑白质和灰质结构中许多活跃的发育事件。本综述阐述了早产儿中这些发育事件和不成熟障碍。强调了与不成熟发生相关的细胞机制，特别关注前少突胶质细胞。现在显然，广泛分布的激活小胶质细胞和反应性星形胶质细胞在不成熟中起着核心作用。由于这些不成熟的细胞机制似乎发生在相对较长的时间窗口内，因此似乎有可能进行预防或改善不成熟的干预，即神经修复干预。这些干预包括药物治疗，特别是促红细胞生成素，并且还特别关注牛奶的质量和来源、母乳喂养、多不饱和脂肪酸、铁和锌等营养因素。最近的研究还表明，针对新生儿期和婴儿期各种体验因素的干预措施在增强大脑发育方面具有强大作用，例如提供最佳的听觉和视觉刺激、最大程度地减少疼痛和压力，以及各种其他环境行为丰富化手段。
