Impact of inflammation on developing respiratory control networks: rhythm generation, chemoreception and plasticity.
Impact of inflammation on developing respiratory control networks: rhythm generation, chemoreception and plasticity.
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DOI：
10.1016/j.resp.2019.103357
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发表时间：
2020-03
影响因子：
2.3
通讯作者：
Huxtable AG
中科院分区：
文献类型：
--
作者：
Beyeler SA;Hodges MR;Huxtable AG
中枢神经系统中的呼吸控制网络在生命早期经历关键的发育事件，以确保出生时充足的呼吸。呼吸控制网络的发育至少有三个“关键窗口”：1）子宫内，2）新生儿（啮齿动物出生后0-4天），3）新生儿（啮齿动物P10-13，人类2-4个月）。在这些关键窗口期间，呼吸控制网络正常成熟所需的发育过程发生，从而增加了网络对炎症等损伤的脆弱性。生命早期炎症（由脂多糖、慢性间歇性缺氧、持续缺氧或新生儿母体分离引起）会严重损害呼吸节律的产生、化学感受并增加新生儿的死亡风险。这些早期生命损伤在年轻男性中也更为严重，表明呼吸控制方面存在性别特异性损伤。此外，新生儿炎症会损害成人呼吸可塑性，从而对呼吸控制产生持久影响。本综述重点关注炎症如何改变三个关键窗口期间的呼吸节律产生、化学感受和可塑性。我们还强调需要进行额外的机制研究，并加强对神经胶质细胞（例如小胶质细胞和星形胶质细胞）如何在炎症后呼吸控制受损中发挥作用的研究。了解发育关键时期的炎症如何破坏呼吸控制网络对于为脆弱的新生儿开发更好的治疗方法和预防成人通气控制障碍至关重要。
The respiratory control network in the central nervous system undergoes critical developmental events early in life to ensure adequate breathing at birth. There are at least three “critical windows” in development of respiratory control networks: 1) in utero, 2) newborn (postnatal day 0–4 in rodents), and 3) neonatal (P10–13 in rodents, 2–4 months in humans). During these critical windows, developmental processes required for normal maturation of the respiratory control network occur, thereby increasing vulnerability of the network to insults, such as inflammation. Early life inflammation (induced by LPS, chronic intermittent hypoxia, sustained hypoxia, or neonatal maternal separation) acutely impairs respiratory rhythm generation, chemoreception and increases neonatal risk of mortality. These early life impairments are also greater in young males, suggesting sex-specific impairments in respiratory control. Further, neonatal inflammation has a lasting impact on respiratory control by impairing adult respiratory plasticity. This review focuses on how inflammation alters respiratory rhythm generation, chemoreception and plasticity during each of the three critical windows. We also highlight the need for additional mechanistic studies and increased investigation into how glia (such as microglia and astrocytes) play a role in impaired respiratory control after inflammation. Understanding how inflammation during critical windows of development disrupt respiratory control networks is essential for developing better treatments for vulnerable neonates and preventing adult ventilatory control disorders.
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