BACKGROUND Recent findings describe microglia as modulators of neurogenesis in the subventricular zone (SVZ). SVZ microglia in the adult rat are thought to adopt a neurotrophic phenotype after ischemic stroke. Early postnatal microglia are endogenously activated and may therefore exhibit an increased sensitivity to neonatal hypoxia-ischemia (HI). The goal of this study was to investigate the impact of cortico-striatal HI on the microglial phenotype, function, and gene expression in the early postnatal SVZ. METHODS Postnatal day (P)7 rats underwent sham or right-hemispheric HI surgery. Microglia in the SVZ, the uninjured cortex, and corpus callosum were immunohistochemically analyzed at P10, P20, and P40. The transcriptome of microdissected SVZ and cortical microglia was analyzed at P10 and P20, and the effect of P10 SVZ microglia on neurosphere generation in vitro was studied. RESULTS The microglial response to HI was region-specific. In the SVZ, a microglial accumulation, prolonged activation and phagocytosis was noted that was not observed in the cortex and corpus callosum. The transcriptome of SVZ microglia and cortical microglia were distinct, and after HI, SVZ microglia concurrently upregulated pro- and anti-inflammatory as well as neurotrophic genes. In vitro, microglia isolated from the SVZ supported neurosphere generation in a concentration-dependent manner. CONCLUSIONS Microglia are an inherent cellular component of the early postnatal SVZ and undergo developmental changes that are affected on many aspects by neonatal HI injury. Our results demonstrate that early postnatal SVZ microglia are sensitive to HI injury and display a long-lasting region-specific response including neurotrophic features.

中文翻译：

---

大鼠新生儿缺氧缺血会在 SVZ 小胶质细胞中引发区域特异性神经营养反应。


背景最近的研究结果将小胶质细胞描述为脑室下区（SVZ）神经发生的调节剂。成年大鼠的 SVZ 小胶质细胞被认为在缺血性中风后采用神经营养表型。出生后早期小胶质细胞被内源性激活，因此可能表现出对新生儿缺氧缺血（HI）的敏感性增加。本研究的目的是探讨皮质纹状体 HI 对出生后早期 SVZ 中小胶质细胞表型、功能和基因表达的影响。方法 出生后第 7 天的大鼠接受假手术或右半球 HI 手术。在 P10、P20 和 P40 时对 SVZ、未受伤皮质和胼胝体中的小胶质细胞进行免疫组织化学分析。对 P10 和 P20 时显微解剖的 SVZ 和皮质小胶质细胞的转录组进行分析，并研究 P10 SVZ 小胶质细胞对体外神经球生成的影响。结果 小胶质细胞对 HI 的反应具有区域特异性。在 SVZ 中，注意到小胶质细胞积聚、延长的激活和吞噬作用，而在皮质和胼胝体中未观察到。 SVZ 小胶质细胞和皮质小胶质细胞的转录组是不同的，HI 后，SVZ 小胶质细胞同时上调促炎和抗炎以及神经营养基因。在体外，从 SVZ 中分离出的小胶质细胞以浓度依赖性方式支持神经球的生成。结论 小胶质细胞是出生后早期 SVZ 的固有细胞成分，并经历发育变化，这些变化在许多方面受到新生儿 HI 损伤的影响。我们的结果表明，出生后早期 SVZ 小胶质细胞对 HI 损伤敏感，并表现出持久的区域特异性反应，包括神经营养特征。