Background: Experimental studies have shown that Curcumin exerts neuroprotective effects in animal models with middle cerebral artery occlusion (MCAO). However, the mechanisms of protective effects of Curcumin in MCAO are not fully understood. Objective: This study aims to investigate the neurogenesis key targets of Curcumin action in mouse brain with MCAO. Methods: The MCAO models were established in mice. High-Throughput Sequencing was used to identify differentially expressed mRNA, lncRNA and circRNA. The reverse expressed mRNAs, lncRNA and circRNA in sham vs. MCAO and MCAO vs. Curcumin were identified. Biological functions were determined by gene ontology (GO) analyses. The protein-protein interaction (PPI) network of neurogenesis related genes was constructed. Next, neurogenesis related lncRNA/circRNA-miRNA-mRNA ceRNA network were constructed. Results: The total of reverse expressed 1215 mRNAs, 32 lncRNAs, and 43 circRNAs were filtered based on the 2 series (sham vs. MCAO and MCAO vs. Curcumin). The functional enrichment of 1215 reverse expressed mRNAs were involved in neurogenesis, generation of neurons, regulation of neurogenesis and others. The PPI network of neurogenesis related genes consisted of 115 nodes, and including Curcumin down regulated 27 genes and upregulated 36 genes. Further, the neurogenesis related lncRNA/circRNA-miRNA-mRNA ceRNAs network were constructed, and 5 lncRNA ceRNA network and 3 circRNA ceRNA network were explored. Conclusion: Our study revealed that Curcumin exerts neuroprotective effects by regulating neurogenesis. The neurogenesis related lncRNA/circRNA-miRNA-mRNA ceRNA network are potential therapeutic targets of Curcumin in MCAO. This study provided a theoretical basis for Curcumin exerts neuroprotective effects in MCAO.

IntroductionEnlarged perivascular spaces (EPVS) are ubiquitous in the elderly and have insidious onset characteristics. Its correlation with clinical symptoms is easily overlooked and controversial. The related clinical symptoms that EPVS may cause were studied using Meta-analysis.Material and methodsRelevant studies up to April 2022 were extracted from PubMed, Embase, Cochrane, OVID, and Web of Science. Odds ratios (ORs) and 95% confidence interval (CI) were used to estimate the strength of the correlation.ResultsOf the 6622 articles identified, 32 studies were eligible, enrolling a total of 19987 people. EPVS was associated with the risk of cognitive impairment (OR: 1.60, 95 % CI: 1.39- 1.81), motor impairment (OR: 2.24, 95 % CI: 1.22- 3.25), sleep disturbance (OR: 1.81, 95% CI: 1.34-2.28), depressive symptoms (OR: 1.54, 95 % CI: 1.14- 1.95), but was not significantly associated with the occurrence of stroke ( OR: 0.97, 95 % CI: 0.74-1.21). Results of subgroup analysis showed that basal ganglia (BG) EPVS were more associated with cognitive impairment (OR: 2.19, 95% CI: 1.72- 2.65) and sleep disturbance(OR: 1.74, 95 % CI: 1.20- 2.29).ConclusionsOur findings suggested that people with EPVS may be at a greater risk for cognitive impairment, motor impairment, sleep disturbance, and depressive symptoms. This will inform future treatments.