Abstract: Circulating microRNAs (miRNA) have emerged as useful biomarkers for their stability and tissue specificity. However, miRNA studies in dogs with acute spinal cord injury (SCI) from intervertebral disc herniation are limited.
We hypothesized that circulating miRNA reflects injury severity and cell type specificity in a severity-dependent manner.
20 serum samples of 13 dogs with SCI with various severity from a hospital population and 7 healthy control dogs.
Retrospective study. The miRNA was isolated and used for library preparation. Libraries were pooled and sequenced using NovaSeq SP-PE50 to generate 10 million sequences. Post-sequence pipeline was generated. Sample-to-sample distance map and principal component analysis (PCA) from each severity group were performed. Volcano plot analyses were performed to identify differentially expressed (DE) miRNAs. In silico analysis further categorized DE miRNAs by their potential cell type sources by cross-referencing with miRNA database obtained from rodent motor neurons (MN), astrocytes (ASC), and microglia (MG).
PCA demonstrated severity-dependent grouping of miRNA profiles. We identified 94 (mild), 134 (moderate), and 141 (severe) DE miRNAs including 48 (severe), 32 (moderate), and 15 (mild) unique to each severity. In the severe group, we identified 35 down-regulated and 13 up-regulated unique miRNAs that originated from ASC (32 miRNAs), MG (7 miRNAs), and MN (12 miRNAs).
Combined results indicate that circulating miRNAs are promising biomarkers to evaluate SCI injury severities. Further studies elucidating the role of cell type-specific miRNA biomarkers and their correlation with the long-term functional outcome will provide valuable knowledge to develop novel therapeutic approaches in the SCI.
