Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China.
Exp Biol Med (Maywood). 2023 May;248(10):883-896. doi: 10.1177/15353702231157922. Epub 2023 Apr 3.
Poststroke cognitive impairment (PSCI) often occurs during the stroke recovery period and greatly increases the difficulty of rehabilitation. Activation of neuroinflammation and long-term changes in gene expression patterns in the hippocampus could be essential in the development of PSCI. Therefore, this study aimed to identify neuroinflammation and changes in gene expression patterns in the hippocampus in rats with PSCI. Rats underwent transient middle cerebral artery occlusion (tMCAO) or sham surgery. The infarct volume was measured on day 3 after surgery. The Morris water maze (MWM) test was used to assess cognitive function. Microglial activation and white matter (WM) lesions in the hippocampus were evaluated on day 28 after surgery. In addition, we compared differentially expressed genes (DEGs) in the hippocampus between tMCAO group rats and sham group rats by RNA sequencing. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analyses were conducted to investigate these DEGs. The results showed that the tMCAO group rats showed extensive infarction and cognitive dysfunction compared with the sham group rats. Microglial activation and WM damage were obvious in the hippocampus of tMCAO group rats. We found 43 DEGs by RNA sequencing: 29 genes with upregulated expression and 14 genes with downregulated expression. The GO analysis indicated that DEGs were mainly involved in cell proliferation and differentiation, cholesterol synthesis, and metabolism. The KEGG pathway analysis suggested that the DEGs were significantly enriched in intestinal immune network for IgA production and steroid biosynthesis. Acta2, Calb2, and Cxcl12 were notable in the PPI analysis. Our results suggest that microglial activation and WM damage are maintained in rats with PSCI. The mechanism may be related to the regulation of steroid biosynthesis, intestinal immunity, and potential key genes such as Acta2, Calb2, and Cxcl12 in the hippocampus.
卒中后认知障碍（PSCI）常发生于卒中恢复期，极大地增加了康复难度。海马神经炎症的激活和基因表达模式的长期变化可能是 PSCI 发展的关键。因此，本研究旨在确定 PSCI 大鼠海马中的神经炎症和基因表达模式变化。大鼠接受短暂性大脑中动脉闭塞（tMCAO）或假手术。术后第 3 天测量梗死体积。Morris 水迷宫（MWM）测试用于评估认知功能。术后第 28 天评估海马小胶质细胞激活和白质（WM）损伤。此外，我们通过 RNA 测序比较 tMCAO 组大鼠和假手术组大鼠海马中的差异表达基因（DEGs）。然后，进行基因本体论（GO）、京都基因与基因组百科全书（KEGG）和蛋白质-蛋白质相互作用（PPI）网络分析以研究这些 DEGs。结果显示，与假手术组大鼠相比，tMCAO 组大鼠表现出广泛的梗死和认知功能障碍。tMCAO 组大鼠海马中小胶质细胞激活和 WM 损伤明显。通过 RNA 测序发现 43 个 DEGs：29 个基因上调表达，14 个基因下调表达。GO 分析表明，DEGs 主要参与细胞增殖和分化、胆固醇合成和代谢。KEGG 通路分析表明，DEGs 显著富集于 IgA 产生的肠道免疫网络和类固醇生物合成。PPI 分析中，Acta2、Calb2 和 Cxcl12 显著。我们的结果表明，PSCI 大鼠海马中的小胶质细胞激活和 WM 损伤持续存在。其机制可能与类固醇生物合成、肠道免疫以及 Acta2、Calb2 和 Cxcl12 等潜在关键基因的调节有关。
