Increased miR‐124‐3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons

摘要: Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after brain injury (TBI). Inhibiting excessive inflammatory response essential for improving outcome. To clarify regulatory mechanism microglial exosomes on neuronal in TBI, we focused studying impact exosomal miRNAs injured neurons this research. We used a repetitive (r)TBI mouse model harvested extracts from to phase TBI treat cultured BV2 microglia vitro The were collected miRNA microarray analysis, which showed that expression level miR-124-3p increased most apparently miRNAs. found promoted anti-inflamed M2 polarization microglia, inhibited scratch-injured neurons. Further, mammalian target rapamycin (mTOR) signaling was implicated as being involved regulation by Gene Ontology Kyoto Encyclopedia Genes Genomes pathway analyses. Using mTOR activator MHY1485 confirmed inhibitory effect exerted suppressing activity signaling. PDE4B predicted be gene analysis. proved it directly targeted with luciferase reporter assay. overexpressed lentivirus transfection system, suggested suppressed mainly through inhibiting PDE4B. In addition, neurite outgrowth scratch injury, characterized an increase number branches total length, decreased RhoA neurodegenerative proteins [Aβ-peptide p-Tau]. It also improved outcome neuroinflammation mice rTBI. Taken together, can inhibit contribute via their transfer into these effects targeting PDE4B, thus Therefore, could promising therapeutic interventions TBI. manipulated may provide novel therapy other diseases.-Huang, S., Ge, X., Yu, J., Han, Z., Yin, Li, Y., Chen, F., Wang, H., Zhang, Lei, P. Increased following inhibits contributes