Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing 400038, China; Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing 400038, China.
Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing 400038, China; Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing 400038, China; Department of Emergency, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China.
Exp Neurol. 2021 Jul;341:113688. doi: 10.1016/j.expneurol.2021.113688. Epub 2021 Mar 11.
Increasing numbers of patients with spontaneous subarachnoid hemorrhage(SAH) who recover from surgery and intensive care management still live with cognitive impairment after discharge, indicating the importance of white matter injury at the acute stage of SAH. In the present study, standard endovascular perforation was employed to establish an SAH mouse model, and a microRNA (miRNA) chip was used to analyze the changes in gene expression in white matter tissue after SAH. The data indicate that 17 miRNAs were downregulated, including miR-706, miR-669a-5p, miR-669p-5p, miR-7116-5p and miR-195a-3p, while 13 miRNAs were upregulated, including miR-6907-5p, miR-5135, miR-6982-5p, miR-668-5p, miR-8119. Strikingly, miR-706 was significantly downregulated with the highest fold change. Further experiments confirmed that miR-706 could alleviate white matter injury and improve neurological behavior, at least partially by inhibiting the PKCα/MST1/NF-κB pathway and the release of inflammatory cytokines. These results might provide a deeper understanding of the pathophysiological processes in white matter after SAH, as well as potential therapeutic strategies for the translational research.
越来越多的自发性蛛网膜下腔出血（SAH）患者在手术后和重症监护管理下康复，但仍在出院后存在认知障碍，这表明 SAH 急性期的白质损伤很重要。在本研究中，采用标准的血管内穿孔方法建立了一个 SAH 小鼠模型，并使用 microRNA（miRNA）芯片分析了 SAH 后白质组织中基因表达的变化。数据表明，有 17 个 miRNA 下调，包括 miR-706、miR-669a-5p、miR-669p-5p、miR-7116-5p 和 miR-195a-3p，而 13 个 miRNA 上调，包括 miR-6907-5p、miR-5135、miR-6982-5p、miR-668-5p、miR-8119。值得注意的是，miR-706 下调最为显著，倍数变化最大。进一步的实验证实，miR-706 可以减轻白质损伤，改善神经行为，至少部分是通过抑制 PKCα/MST1/NF-κB 通路和炎症细胞因子的释放。这些结果可能为深入了解 SAH 后白质的病理生理过程以及转化研究中的潜在治疗策略提供了依据。
