Identification of candidate genes and pathways in dexmedetomidine-induced neuroprotection in rats using RNA sequencing and bioinformatics analysis.

Background: Traumatic brain injury (TBI) is a major cause of disability worldwide, without definitive and effective intervention. Dexmedetomidine (DEX) has a neuroprotective effect against TBI; however, the detailed mechanism underlying this effect remains unclear.

Methods: Ten male Sprague Dawley rats were used to establish a TBI model. The rats were randomly divided into two groups: the TBI group (TBI, control group) and the DEX treatment group (DEX). The next day, the neurological function of the rats were evaluated by the modified neurological severity score (mNSS). Then, the rats were sacrificed, and RNA sequencing was performed to identify differentially expressed messenger RNAs (mRNAs) and microRNAs (miRNAs) in brain tissue samples. Additionally, we performed a bioinformatics analysis to explore the candidate genes and pathways that might play important roles in DEX-induced neuroprotection. The most significantly differentially expressed miRNAs and possible hub genes were validated by quantitate reverse transcription-polymerase chain reaction (qRT-PCR) using more samples.

Results: In the DEX group, 517 mRNAs (352 up-regulated and 165 down-regulated) and 35 miRNAs (18 up-regulated and 17 down-regulated) were differentially expressed compared to the TBI group. Gene Ontology analysis revealed the up-regulated mRNAs to be significantly enriched in microtubule-based movement or processes, microtubule and tubulin binding. Kyoto Encyclopedia of Genes and Genomes analysis showed that these up-regulated mRNAs were significantly enriched in the B-cell receptor signaling pathway as well as the cell cycle pathway. Also, Lyn and Cdk1 were found to be associated with the B-cell receptor signaling and cell cycle pathways, respectively. Furthermore, the down-regulated miRNAs were significantly enriched in cellular components, although no significant Gene Ontology terms or KEGG pathways were found for the down-regulated mRNAs or up-regulated miRNAs.

Conclusions: Differentially expressed mRNAs and miRNAs were identified after the administration of DEX in a TBI rat model. The B-cell receptor signaling pathway and the cell cycle pathway might be involved in the neuroprotective effect of DEX against TBI, Lyn and Cdk1 might be hub genes.