Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
Axe Neurosciences, Centre de recherche du CHU de Québec-Université Laval, 2705 Boulevard Laurier, Québec, QC, Canada.
Neuroscience. 2019 May 1;405:68-76. doi: 10.1016/j.neuroscience.2018.01.023. Epub 2018 Jan 17.
Microglial cells are now recognized as the "gate-keepers" of healthy brain microenvironment with their disrupted functions adversely affecting neurovascular integrity, neuronal homeostasis, and network connectivity. The perception that these cells are purely toxic under neurodegenerative conditions has been challenged by a continuously increasing understanding of their complexity, the existence of a broad array of microglial phenotypes, and their ability to rapidly change in a context-dependent manner to attenuate or exacerbate injuries of different nature. Recent studies have demonstrated that microglial cells exert crucial physiological functions during embryonic and postnatal brain development, some of these functions being unique to particular stages of development, and extending far beyond sensing dangerous signals and serving as antigen presenting cells. In this focused review we cover the roles of microglial cells in regulating embryonic vasculogenesis, neurogenesis, and establishing network connectivity during postnatal brain development. We further discuss context-dependent microglial contribution to neonatal brain injuries associated with prenatal and postnatal infection and inflammation, in relation to neurodevelopmental disorders, as well as perinatal hypoxia-ischemia and arterial focal stroke. We also emphasize microglial phenotypic diversity, notably at the ultrastructural level, and their sex-dependent influence on the pathophysiology of neurodevelopmental disorders.
小胶质细胞现在被认为是健康脑微环境的“守门员”，其功能障碍会对神经血管完整性、神经元内稳态和网络连接产生不利影响。人们一直认为这些细胞在神经退行性疾病条件下纯粹是有毒的，但随着对其复杂性、广泛存在的小胶质细胞表型以及它们能够快速、依赖于上下文的方式改变以减轻或加剧不同性质损伤的能力的不断深入理解，这种看法受到了挑战。最近的研究表明，小胶质细胞在胚胎和出生后大脑发育过程中发挥着至关重要的生理功能，其中一些功能是特定发育阶段所特有的，并且远远超出了感知危险信号和作为抗原呈递细胞的作用。在本次重点综述中，我们将讨论小胶质细胞在调节胚胎血管生成、神经发生以及出生后大脑发育过程中建立网络连接方面的作用。我们还进一步讨论了与神经发育障碍相关的围产期感染和炎症、新生儿脑损伤以及围产期缺氧缺血和动脉局灶性中风中小胶质细胞在特定背景下的作用。我们还强调了小胶质细胞表型多样性，特别是在超微结构水平上，以及它们对神经发育障碍病理生理学的性别依赖性影响。
