Infections in the Developing Brain: The Role of the Neuro-Immune Axis.
Infections in the Developing Brain: The Role of the Neuro-Immune Axis.
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DOI：
10.3389/fneur.2022.805786
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发表时间：
2022
影响因子：
3.4
通讯作者：
Tucker EW
中科院分区：
文献类型：
--
作者：
Kim J;Erice C;Rohlwink UK;Tucker EW
中枢神经系统（CNS）感染在幼儿中比成人更常见，对发育中的大脑构成独特的挑战。这篇综述建立在儿童外周免疫系统的独特脆弱性（在本综述系列的第1部分中概述）的基础上，重点关注一旦发生CNS感染，发育中的大脑如何反应。虽然保护性血脑屏障（BBB）成熟较早，但病原体进入CNS并启动局部先天性免疫应答，释放细胞因子和趋化因子以募集有助于炎症级联反应的外周免疫细胞。这种免疫反应是由常驻脑细胞，小胶质细胞和星形胶质细胞启动的，它们不仅是对抗感染的组成部分，而且在正常的大脑发育过程中也具有重要作用。此外，细胞因子和其他免疫介质如来自神经元、神经胶质和内皮细胞的基质金属蛋白酶不仅在BBB渗透性和外周细胞募集中起作用，而且在脑成熟中起作用。因此，这些免疫调节剂和感染期间小胶质细胞和星形胶质细胞的活化对正常的神经发育产生不利影响。正常大脑发育的干扰表现为神经发育和神经认知障碍，在CNS感染存活的儿童中常见，并且通常是永久性的。在综述系列的第2部分中，我们广泛总结了CNS感染在发育中的大脑中产生的独特挑战，并探讨了神经发育和CNS免疫反应调节因子作为神经免疫轴的一部分的相互作用。
Central nervous system (CNS) infections occur more commonly in young children than in adults and pose unique challenges in the developing brain. This review builds on the distinct vulnerabilities in children's peripheral immune system (outlined in part 1 of this review series) and focuses on how the developing brain responds once a CNS infection occurs. Although the protective blood-brain barrier (BBB) matures early, pathogens enter the CNS and initiate a localized innate immune response with release of cytokines and chemokines to recruit peripheral immune cells that contribute to the inflammatory cascade. This immune response is initiated by the resident brain cells, microglia and astrocytes, which are not only integral to fighting the infection but also have important roles during normal brain development. Additionally, cytokines and other immune mediators such as matrix metalloproteinases from neurons, glia, and endothelial cells not only play a role in BBB permeability and peripheral cell recruitment, but also in brain maturation. Consequently, these immune modulators and the activation of microglia and astrocytes during infection adversely impact normal neurodevelopment. Perturbations to normal brain development manifest as neurodevelopmental and neurocognitive impairments common among children who survive CNS infections and are often permanent. In part 2 of the review series, we broadly summarize the unique challenges CNS infections create in a developing brain and explore the interaction of regulators of neurodevelopment and CNS immune response as part of the neuro-immune axis.
DOI：
10.1007/s00018-020-03563-2
发表时间：
2021-03
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Carriba P;Davies AM
通讯作者：
Davies AM