Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.
Neurochem Res. 2021 Feb;46(2):276-286. doi: 10.1007/s11064-020-03161-5. Epub 2020 Nov 2.
Poststroke cognitive impairment (PSCI) is one of the most severe sequelae of stroke and lacks effective treatment. Previous studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) may be a promising PSCI therapeutic approach, but the underlying mechanism is unclear. To uncover the effect of rTMS on PSCI, a transient middle cerebral artery occlusion (tMCAO) model was established. Modified Neurological Severity Score (mNSS) test and Morris Water Maze (MWM) test were performed to assess the neurological and cognitive function of rats. Furthermore, to explore the underlying mechanism, differentially expressed genes (DEGs) in the hippocampus of rats in the rTMS group and tMCAO group were compared using RNA sequencing. Then, bioinformatics analysis, including gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis, was conducted to elaborate these DEGs. Our results indicated that high-frequency rTMS could significantly improve neurological and cognitive function, according to mNSS and MWM tests. We found 85 DEGs, including 71 upregulated genes and 14 downregulated genes, between the rTMS group and tMCAO group. The major functional category was related to chemical synaptic transmission modulation and several DEGs were significantly upregulated in processes related to synaptic plasticity, such as glutamatergic synapses. Calb2, Zic1, Kcnk9, and Grin3a were notable in PPI analysis. These results demonstrate that rTMS has a beneficial effect on PSCI, and its mechanism may be related to the regulation of synaptic plasticity and functional genes such as Calb2, Zic1, Kcnk9, and Grin3a in the hippocampus.
卒中后认知障碍（PSCI）是卒中最严重的后遗症之一，目前缺乏有效的治疗方法。既往研究表明，高频重复经颅磁刺激（rTMS）可能是一种有前途的 PSCI 治疗方法，但作用机制尚不清楚。为了揭示 rTMS 对 PSCI 的影响，建立了短暂性大脑中动脉闭塞（tMCAO）模型。通过改良神经功能缺损评分（mNSS）试验和 Morris 水迷宫（MWM）试验评估大鼠的神经和认知功能。此外，为了探讨其潜在机制，采用 RNA 测序比较 rTMS 组和 tMCAO 组大鼠海马中的差异表达基因（DEGs）。然后，通过基因本体（GO）分析、京都基因与基因组百科全书（KEGG）分析和蛋白质-蛋白质相互作用（PPI）网络分析等生物信息学分析，阐述这些 DEGs。结果表明，高频 rTMS 可明显改善 mNSS 和 MWM 试验大鼠的神经和认知功能。我们发现 rTMS 组和 tMCAO 组之间有 85 个 DEGs，包括 71 个上调基因和 14 个下调基因。主要功能类别与化学突触传递调节有关，一些 DEGs 在与突触可塑性相关的过程中显著上调，如谷氨酸能突触。PPI 分析中，Calb2、Zic1、Kcnk9 和 Grin3a 比较显著。这些结果表明，rTMS 对 PSCI 具有有益作用，其机制可能与调节海马中突触可塑性和功能基因（如 Calb2、Zic1、Kcnk9 和 Grin3a）有关。
