Transcriptomic characterization of microglia activation in a rat model of ischemic stroke
Transcriptomic characterization of microglia activation in a rat model of ischemic stroke
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DOI：
10.1177/0271678x20932870
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发表时间：
2020-06-17
影响因子：
6.3
通讯作者：
Xing, Changhong
中科院分区：
文献类型：
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作者：
Deng, Wenjun;Mandeville, Emiri;Xing, Changhong
小胶质细胞是中风和脑损伤后炎症反应的关键调节因子。为了更好地了解缺血性卒中后小胶质细胞的激活及其表型多样性，我们分析了3个月和12个月大的雄性自发性高血压大鼠75分钟短暂局灶性脑缺血后小胶质细胞的转录组。在脑缺血后第3天和第14天通过FACS分选从脑中分离小胶质细胞。使用GeneChip Rat 1.0ST微阵列来分析分选的小胶质细胞的全转录组。我们确定了一个不断发展的和复杂的激活模式，从中风发作后3至14天。随着时间的推移，M2样模式广泛且持续上调。M1样模式仅轻度上调，主要在第14天。与年龄较大的12个月大的大脑相比，年龄较小的3个月大的大脑在促炎和抗炎通路中表现出更大的小胶质细胞反应。重要的是，我们的数据显示，中风后，大多数小胶质细胞被激活，朝向超出标准M1/M2二分法的广谱新极化状态，特别是在与TLR 2和膳食脂肪酸信号传导相关的通路中。最后，确定了可能潜在调节小胶质细胞激活的转录因子类别。这些研究结果应该提供一个全面的数据库，解剖小胶质细胞机制和追求急性缺血性卒中的神经炎症目标。
Microglia are key regulators of inflammatory response after stroke and brain injury. To better understand activation of microglia as well as their phenotypic diversity after ischemic stroke, we profiled the transcriptome of microglia after 75 min transient focal cerebral ischemia in 3-month- and 12-month-old male spontaneously hypertensive rats. Microglia were isolated from the brains by FACS sorting on days 3 and 14 after cerebral ischemia. GeneChip Rat 1.0ST microarray was used to profile the whole transcriptome of sorted microglia. We identified an evolving and complex pattern of activation from 3 to 14 days after stroke onset. M2-like patterns were extensively and persistently upregulated over time. M1-like patterns were only mildly upregulated, mostly at day 14. Younger 3-month-old brains showed a larger microglial response in both pro- and anti-inflammatory pathways, compared to older 12-month-old brains. Importantly, our data revealed that after stroke, most microglia are activated towards a wide spectrum of novel polarization states beyond the standard M1/M2 dichotomy, especially in pathways related to TLR2 and dietary fatty acid signaling. Finally, classes of transcription factors that might potentially regulate microglial activation were identified. These findings should provide a comprehensive database for dissecting microglial mechanisms and pursuing neuroinflammation targets for acute ischemic stroke.