极早产儿脑干-小脑呼吸网络的易损性

文献信息

中文摘要

背景： 过去数十年间，极早产儿的存活率显著提高，使呼吸和脑发育的关键阶段转移至宫外环境。这一转变使脆弱的早产儿暴露于氧张力骤变、间歇性低氧血症、炎症和氧化应激，从而导致包括脑和脑干在内的未成熟器官结构和功能发育不良，并带来短期和长期不良后果。本综述探讨极低胎龄新生儿（ELGANs，出生时胎龄<28周）在关键发育期遭受的不良宫内和宫外暴露如何破坏中枢呼吸网络关键组件的结构和功能，并支持流行病学证据，即早产儿在出生后第一年发生婴儿猝死综合征（SUID）的风险显著增加，且终生存在睡眠呼吸障碍。结果：ELGANs出生时正值脑干和小脑快速发育期，使这些区域更易受到氧化和炎症损伤，从而造成直接组织损伤和发育异常。延髓5-羟色胺能网络和小脑顶核调节静息状态以及进行性低氧和高碳酸血症期间的心肺反应。我们提出，关键发育窗口期的不良宫内和宫外暴露会损害这些区域的大体和微观结构及神经化学，削弱保护性呼吸反应，并在机制上导致ELGANs发生SUID的风险比足月儿高2至3倍。我们综述了胎儿对低氧的神经保护反应；ELGANs脑损伤的机制和易损性；中枢呼吸控制的发展及其内在低氧化学敏感性；以及脑干和小脑发育异常。结论：总之，这一框架提供了将极早产与通气控制受损、呼吸紊乱以及婴儿期及以后猝死易感性增加联系起来的生物学基础。

英文摘要

Survival of extremely preterm infants has significantly improved over the past decades, shifting critical stages of respiratory and brain development into the extrauterine environment. This transition exposes the vulnerable preterm infant to abrupt changes in oxygen tension, intermittent hypoxemia, inflammation, and oxidative stress, which contribute to maldevelopment of the structure and function of immature organs, including the brain and brainstem, with short- and long-term adverse consequences. This review examines how adverse intrauterine and extrauterine exposures during critical developmental periods in extremely low gestational age neonates (ELGANs) born <28 weeks of gestation disrupt the structure and function of key components of the central respiratory network, supporting epidemiological evidence that premature infants have a substantially increased risk of sudden unexpected infant death (SUID) during the first year of life and sleep disordered breathing across the lifespan. ELGANs are born during a period of rapid brainstem and cerebellar development, increasing the vulnerability of these regions to oxidative and inflammatory injury that can cause direct tissue damage and dysmaturation. The medullary serotonergic network and cerebellar fastigial nucleus regulate cardiorespiratory responses at rest and during progressive hypoxia and hypercapnia. We propose that adverse intrauterine and extrauterine exposures during critical developmental windows damage the macro- and microstructures, neurochemistry of these regions, impair protective respiratory responses, and mechanistically contribute to the two- to threefold higher risk of SUID in ELGANs than in term infants. We review fetal neuroprotective responses to hypoxia; the mechanisms and vulnerability of brain injury in ELGANs; the development and intrinsic hypoxic chemosensitivity of central respiratory control; and brainstem and cerebellar dysmaturation. Together, this framework provides a biological basis linking extreme prematurity to impaired ventilatory control, disordered breathing, and increased vulnerability to sudden death during infancy and beyond.