Integrated Analysis of Porcine Brain microRNA Profiles Following Pediatric Diffuse Traumatic Brain Injury

Interestingly, many miRNAs involved in disrupted neuronal and upregulated glial, epithelial, and endothelial functions were differentially expressed (DE-miRNAs) at 1 day post-injury and most returned to baseline by 1 week post-injury. However, miR-20a-3p, miR-10386, and miR-4331-3p were among the Top 10 DE-miRNAs at 1 day post-injury, and remained altered at 1 week. Upregulated neuroprotective miR-17-3p and miR-212 were also part of Top 10 DE-miRNAs at 1 day post-injury and their increases were correlated with decreases in axonal injury.

Furthermore, to identify miRNAs that could serve as candidate diagnostic biomarkers of injury, we employed LASSO analysis and identified miRNAs, miR-363, miR-15b, and miR-450c-3p as the best predictors of mTBI at 1 day post-injury. Lastly, WGCNA revealed the neuroprotective effects of CsA treatment in ameliorating neuronal, immune, stress, and vascular functions disrupted at 1 day post-injury. Overall, our data revealed key miRNAs that were differentially expressed at 1 day and 1 week post-injury, modulated by CsA treatment, and suggest that may serve as diagnostic biomarkers of pediatric mTBI.