Altered expression of MiR-186-5p and its target genes after spinal cord ischemia-reperfusion injury in rats.

Spinal cord ischemia-reperfusion (I/R) injury remains an unresolved problem, and the mechanism is not fully elaborated. In a rat model of spinal cord I/R injury, we performed microarray analysis to examine the altered expression of microRNAs (miRs) at 24 h after the modelling. miR-186-5p was chosen for further study. An miR mimic or anti-miR oligonucleotide was intrathecally infused before the surgical procedure. The participation of miR-186-5p and its potential target genes based on bioinformatics analysis were analysed next. Pre-treatment with the miR-186-5p mimic improved neurological function and histological assessment scores; reduced Evans Blue extravasation; attenuated spinal cord oedema; and decreased interleukin 15 (IL-15), IL-6, IL-1β, and tumour necrosis factor-α (TNF-α) expression at 24 h after the modelling. KEGG analysis showed that the group of potential target genes of miR-186-5p was notably enriched in several signalling cascades, such as the Wnt, Hippo, and PI3K-AKT pathways. Gene Ontology (GO) analysis revealed that the group of potential target genes of miR-186-5p was significantly enriched in several biological processes, such as 'Wnt signalling pathway', 'regulation of inflammatory response', and 'Toll-like receptor signalling pathway'. We further found that Wnt5a, TLR3, and chemokine (C-X-C motif) ligand 13 (CXCL13) were upregulated after the modelling and the miR-186-5p mimic reduced the induction of the aforementioned target genes. These data provide evidence that upregulation of miR-186-5p improves neurological outcomes induced by spinal cord I/R injury and may inhibit neuroinflammation through Wnt5a-, TLR3-, or CXCL13-mediated signal pathway in spinal cord I/R injury.