Perinatal brain injuries, including encephalopathy related to fetal growth restriction, encephalopathy of prematurity, neonatal encephalopathy of the term neonate, and neonatal stroke, are a major cause of neurodevelopmental disorders. They trigger cellular and molecular cascades that lead in many cases to permanent motor, cognitive, and/or behavioral deficits. Damage includes neuronal degeneration, selective loss of subclasses of interneurons, blocked maturation of oligodendrocyte progenitor cells leading to dysmyelination, axonopathy and very likely synaptopathy, leading to impaired connectivity. The nature and severity of changes vary according to the type and severity of insult and maturation stage of the brain. Microglial activation has been demonstrated almost ubiquitously in perinatal brain injuries and these responses are key cell orchestrators of brain pathology but also attempts at repair. These divergent roles are facilitated by a diverse suite of transcriptional profiles and through a complex dialogue with other brain cell types. Adding to the complexity of understanding microglia and how to modulate them to protect the brain is that these cells have their own developmental stages, enabling them to be key participants in brain building. Of note, not only do microglia help build the brain and respond to brain injury, but they are a key cell in the transduction of systemic inflammation into neuroinflammation. Systemic inflammatory exposure is a key risk factor for poor neurodevelopmental outcomes in preterm born infants. Based on these observations, microglia appear as a key cell target for neuroprotection in perinatal brain injuries. Numerous strategies have been developed experimentally to modulate microglia and attenuate brain injury based on these strong supporting data and we will summarize these.

中文翻译：

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小胶质细胞介导的围产期脑损伤中的神经变性

围产期脑损伤，包括与胎儿生长受限相关的脑病，早产儿脑病，术语新生儿的新生儿脑病和新生儿中风，是神经发育障碍的主要原因。它们触发细胞和分子级联反应，在许多情况下会导致永久性运动，认知和/或行为缺陷。损害包括神经元变性，中间神经元亚类的选择性丧失，少突胶质细胞祖细胞的成熟阻滞，导致髓鞘变性，轴突病和很可能的突触病，从而导致连通性受损。变化的性质和严重程度根据大脑的损伤和成熟阶段的类型和严重程度而有所不同。小胶质细胞激活在围生期脑损伤中几乎无处不在，这些反应是脑病理的关键细胞协调器，也是修复的尝试。这些不同的作用通过多种转录谱套件以及与其他脑细胞类型的复杂对话而得以促进。理解小胶质细胞以及如何调节它们以保护大脑的复杂性在于，这些细胞具有自己的发育阶段，从而使其成为大脑构建的关键参与者。值得注意的是，小胶质细胞不仅有助于建立大脑并对脑损伤做出反应，而且它们是将全身性炎症转化为神经炎症的关键细胞。全身性炎症暴露是早产儿神经发育不良的关键危险因素。基于这些观察，小胶质细胞似乎是围产期脑损伤中神经保护的关键细胞靶标。基于这些有力的支持数据，实验性地开发了许多策略来调节小胶质细胞和减轻脑损伤，我们将对其进行总结。