Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.
Brain Res Bull. 2021 Oct;175:16-25. doi: 10.1016/j.brainresbull.2021.07.012. Epub 2021 Jul 16.
Poststroke cognitive impairment (PSCI) occurs frequently after stroke, but lacks effective treatments. Previous studies have revealed that high-frequency repetitive transcranial magnetic stimulation (rTMS) has a beneficial effect on PSCI and is often used with other cognitive training methods to improve its effect. This study aimed to evaluate the effect of different combinations of rTMS and cognitive training (rTMS-COG) on PSCI and identify the optimal combination protocol. A cerebral infarction rat model was established by transient middle cerebral artery occlusion (tMCAO). The Morris water maze test was conducted to assess the cognitive function of rats. RNA sequencing and bioinformatics analysis were employed to study the underlying mechanisms. rTMS, COG and rTMS-COG all had beneficial effects on PSCI, while cognitive training immediately after rTMS (rTMS-COG) achieved a better effect than cognitive training 1 h and 4 h after rTMS, rTMS and COG. We identified 179 differentially expressed genes (DEGs), including 24 upregulated and 155 downregulated genes, between the rTMS-COG and rTMS groups. GO analysis revealed that the major categories associated with the DEGs were antigen procession and presentation, regulation of protein phosphorylation and axoneme assembly. KEGG analysis showed that the DEGs were enriched in processes related to phagosome, circadian entrainment, dopaminergic synapse, apelin signaling pathway, long-term depression, neuroactive ligand-receptor interaction, axon guidance and glucagon signaling pathway. PPI analysis identified Calb2, Rsph1, Ccdc114, Acta2, Ttll9, Dnah1, Dlx2, Dlx1, Ccdc40 and Ccdc113 as related genes. These findings prompt exploration of the potential mechanisms and key genes involved in the effect of rTMS-COG on PSCI.
卒中后认知障碍（PSCI）在卒中后经常发生，但缺乏有效的治疗方法。先前的研究表明，高频重复经颅磁刺激（rTMS）对 PSCI 有有益的影响，并且经常与其他认知训练方法一起使用以提高其效果。本研究旨在评估 rTMS 和认知训练（rTMS-COG）的不同组合对 PSCI 的影响，并确定最佳组合方案。通过短暂性大脑中动脉闭塞（tMCAO）建立脑梗死大鼠模型。通过 Morris 水迷宫测试评估大鼠的认知功能。进行 RNA 测序和生物信息学分析以研究潜在机制。rTMS、COG 和 rTMS-COG 对 PSCI 均有有益作用，而 rTMS 后立即进行认知训练（rTMS-COG）的效果优于 rTMS 后 1 小时和 4 小时以及单独 rTMS 和 COG 的效果。我们在 rTMS-COG 和 rTMS 组之间鉴定出 179 个差异表达基因（DEGs），包括 24 个上调和 155 个下调基因。GO 分析显示，与 DEGs 相关的主要类别是抗原加工和呈递、蛋白质磷酸化调节和轴丝组装。KEGG 分析表明，DEGs 富集在与吞噬体、昼夜节律同步、多巴胺能突触、apelin 信号通路、长时程抑郁、神经活性配体-受体相互作用、轴突导向和胰高血糖素信号通路相关的过程中。PPI 分析确定了 Calb2、Rsph1、Ccdc114、Acta2、Ttll9、Dnah1、Dlx2、Dlx1、Ccdc40 和 Ccdc113 作为相关基因。这些发现提示我们探索 rTMS-COG 对 PSCI 影响的潜在机制和关键基因。
