Different combinations of high-frequency rTMS and cognitive training improve the cognitive function of cerebral ischemic rats

Abstract

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-COG0h) 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-COG0h 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-COG0h on PSCI.