MicroRNA alteration in cerebrospinal fluid from comatose patients with traumatic brain injury after right median nerve stimulation

Electrical stimulation of the right median nerve can aid coma arousal after traumatic brain injury (TBI). This study aimed to confirm the efficacy further and explore possible mechanisms of right median nerve electrical stimulation (RMNS). Five comatose patients after severe TBI from May to September 2020 in the Tianjin Medical University General Hospital received RMNS for 2 weeks besides standard management. After the 2-week treatment, the mean Glasgow Coma Scale (GCS) and neurophysiological examination were used. We then investigated the alterations in microRNA (miRNA) expression in cerebrospinal fluid (CSF) by high-throughput whole transcriptome sequencing, analyzed the data by Gene Ontology (GO) and pathway analysis, and constructed the miRNA–target gene network. Patient awareness and brain function showed a more rapid increase after treatment. We also found 38 differently expressed miRNAs, 34 of which were upregulated and 4 downregulated. GO analysis showed a relation of these differentially expressed miRNAs with neuronal growth, repair, and neural signal transmission. The most highly correlated pathways were primarily associated with the tumor necrosis factor (TNF) signaling pathway and dopaminergic synapse. The application of RMNS effectively promoted early awakening in comatose patients with severe TBI. Moreover, differentially expressed miRNAs might reduce neuronal apoptosis and increase dopamine levels by regulating target gene expression, thus participating in the specific biological process after arousal therapy. Our study provided novel targets for further research on the molecular mechanisms of RMNS arousal treatment and a new way to treat neurotraumatic diseases.