Multiomics profiling of molecular and cellular dynamics of spinal cord injury in a rat [miRNA-seq]
Spinal cord injury (SCI) is a debilitating condition with no effective treatment. The injury triggers a complex cascade of molecular and cellular events that drive both damage and repair processes. To explore these mechanisms, we performed a comprehensive multiomics analysis in a rat compression model of SCI, focusing on the acute phase. Transcriptomic profiling revealed extensive gene dysregulation, highlighting early inflammation, neuronal death, and synaptic dysfunction, followed by the initiation of reparative processes. Cell type composition analysis showed a rapid infiltration of peripheral immune cells, activation of microglia, and loss of neurons, astrocytes, and oligodendrocytes. miRNA profiling uncovered a highly dysregulated miRNA landscape, with the miR-17~92 cluster emerging as a key regulator of neurogenesis, synaptic activity, and cell survival. Integrative miRNA-mRNA-protein analysis identified potential therapeutic targets, including miR-20a, whose inhibition in vitro supported neurogenesis and reduced apoptosis under oxidative stress. Our findings provide new insights into the molecular mechanisms of SCI and highlight miRNAs as potential targets for therapeutic intervention. Overall design: Adult male Wistar rats (n=64) were used as an experimental model. The rats were obtained from the facility's breeding center (Physiological Institute of the Academy of Sciences of the Czech Republic, Prague, Czech Republic). Animals undergoing surgery weighed 300 ± 30 g and were 10 weeks old. Animals were maintained on a 12-h light/dark cycle with ad libitum access to food and water. Rats were randomly divided into experimental groups: SCI 3 hpi (n=4), 12 hpi (n=4), 24 hpi (n=4), 3 dpi (n=4), 7 dpi (n=4), time- corresponding shame-operated groups (n=4 for each group) and an intact control group (n=4), also 8 animals were used for behavioral tests and 12 animals were used for immunohistochemical analysis.