Glaesserella parasuis (G. parasuis) causes serious inflammation and meningitis in piglets. Quercetin has anti-inflammatory and anti-bacterial activities; however, whether quercetin can alleviate brain inflammation and provide protective effects during G. parasuis infection has not been studied. Here, we established a mouse model of G. parasuis infection in vivo and in vitro to investigate transcriptome changes in the mouse cerebrum and determine the protective effects of quercetin on brain inflammation and blood–brain barrier (BBB) integrity during G. parasuis infection. The results showed that G. parasuis induced brain inflammation, destroyed BBB integrity, and suppressed PI3K/Akt/Erk signaling-pathway activation in mice. Quercetin decreased the expression of inflammatory cytokines (Il-18, Il-6, Il-8, and Tnf-α) and BBB-permeability marker genes (Mmp9, Vegf, Ang-2, and Et-1), increased the expression of angiogenetic genes (Sema4D and PlexinB1), reduced G. parasuis-induced tight junction disruption, and reactivated G. parasuis-induced suppression of the PI3K/Akt/Erk signaling pathway in vitro. Thus, we concluded that quercetin may protect BBB integrity via the PI3K/Akt/Erk signaling pathway during G. parasuis infection. This was the first attempt to explore the protective effects of quercetin on brain inflammation and BBB integrity in a G. parasuis-infected mouse model. Our findings indicated that quercetin is a promising natural agent for the prevention and treatment of G. parasuis infection.

Glaesserella parasuis (G. parasuis, GPS) is a known causative agent of meningitis. A growing body of research indicates that non-coding RNAs (ncRNAs) are deeply involved in modulating inflammatory responses. In our study, we profiled the expression changes in circRNAs, lncRNAs, miRNAs, and mRNAs using a G. parasuis-induced mouse meningitis model and constructed the ceRNA networks by integrated analysis of the expression data. A total of 674 circRNAs, 376 lncRNAs, 57 miRNAs, and 373 mRNAs were differentially expressed. Functional GO and KEGG analysis showed enrichment of the source genes of differentially expressed (DE) circRNAs in protein binding, tight junction, and inflammatory pathways such as NF-kappaB, PI3K–Akt, and MAPK. The target genes of DEmiRNAs were enriched in phospholipase D, calcium, Rap1, and mTOR signaling pathways, whereas those of DElncRNAs were largely connected to tight junction, cytokine–cytokine receptor interaction, inflammatory response, and immune system processes. Subsequently, the DEcircRNAs–DEmiRNAs–DEmRNAs ceRNA network consisted of 177 DEcircRNAs, 20 DEmiRNAs, and 134 DEmRNAs, and the DElncRNAs–DEmiRNAs–DEmRNAs ceRNA network consisted of 152 DElncRNAs, 36 DEmiRNAs, and 177 DEmRNAs. Furthermore, the differential expression of randomly selected DEcircRNAs, DElncRNAs, DEmiRNAs, and DEmRNAs was confirmed by qRT-PCR, and the results were consistent with transcriptome sequencing. As far as we know, this study is the first integrative analysis for the ceRNA regulatory networks in G. parasuis-induced mouse meningitis, providing a theoretical basis for elucidating the pathogenic mechanisms of G. parasuis infection.