The neuroinflammation in the ischemic brain could occur as sterile inflammation in response to damage-associated molecular patterns (DAMPs). However, its long-term dynamic transcriptional changes remain poorly understood. It is also unknown whether this neuroinflammation contributes to the recovery or just deteriorates the outcome. The purpose of this study is to characterize the temporal transcriptional changes in the post-stroke brain focusing on DAMPs-related genes by RNA-sequencing during the period of 28 days. We conducted the RNA-sequencing on day 1, 3, 7, 14, 28 post-stroke in the mouse photothrombosis model. The gross morphological observation showed the ischemic lesion on the ipsilateral cortex turned into a scar with the clearance of cellular debris by day 28. The transcriptome analyses indicated that post-stroke period of 28 days was classified into four categories (I Baseline, II Acute, III Sub-acute-#1, IV Sub-acute-#2 phase). During this period, the well-known genes for DAMPs, receptors, downstream cascades, pro-inflammatory cytokines, and phagocytosis were transcriptionally increased. The gene ontology (GO) analysis of biological process indicated that differentially expressed genes (DEGs) are genetically programmed to achieve immune and inflammatory pathways. Interestingly, we found the biphasic induction of various genes, including DAMPs and pro-inflammatory factors, peaking at acute and sub-acute phases. At the sub-acute phase, we also observed the induction of genes for phagocytosis as well as regulatory and growth factors. Further, we found the activation of CREB (cAMP-response element binding protein), one of the key players for neuronal plasticity, in peri-ischemic neurons by immunohistochemistry at this phase. Taken together, these findings raise the possibility the recurrent inflammation occurs at the sub-acute phase in the post-stroke brain, which could be involved in the debris clearance as well as neural reorganization.

中文翻译：

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DAMPs相关基因的时间表达谱揭示了实验性卒中模型中的双相缺血后炎症。

缺血性大脑中的神经炎症可能会作为对损伤相关分子模式（DAMPs）的无菌炎症发生。但是，其长期动态转录变化仍然知之甚少。还不清楚这种神经炎症是否有助于恢复或仅恶化结果。这项研究的目的是在28天的时间内通过RNA测序来表征卒中后大脑中与DAMPs相关基因有关的瞬时转录变化。我们在小鼠光血栓形成模型的中风后第1、3、7、14、28天进行了RNA测序。总体形态学观察显示，到第28天，同侧皮质的缺血性病变变成了疤痕，并清除了细胞碎片。转录组分析表明，卒中后28天分为四类（I基线，II急性，III亚急性-＃1，IV亚急性-＃2期）。在此期间，DAMPs，受体，下游级联，促炎性细胞因子和吞噬作用的众所周知的基因在转录上得以增加。生物过程的基因本体论（GO）分析表明，对差异表达基因（DEG）进行了遗传编程，以实现免疫和炎症途径。有趣的是，我们发现包括DAMPs和促炎因子在内的各种基因的双相诱导均在急性和亚急性期达到峰值。在亚急性期，我们还观察到了吞噬作用基因以及调节因子和生长因子的诱导。进一步，我们在这一阶段通过免疫组织化学发现了周围神经元周围神经元可塑性的关键参与者之一CREB（cAMP反应元件结合蛋白）的激活。综上所述，这些发现增加了复发性炎症发生在中风后大脑亚急性期的可能性，这可能与碎片清除以及神经重组有关。