Multi-omics analysis reveals GABAergic dysfunction after traumatic brainstem injury in rats

Abstract

BackgroundTraumatic brainstem injury (TBSI) is one of the forms of brain injury and has a very high mortality rate. Understanding the molecular mechanism of injury can provide additional information for clinical treatment.Materials and methodsIn this study, we detected transcriptome, proteomics, and metabolome expression changes in the brainstem of TBSI rats, and comprehensively analyzed the underlying mechanisms of TBSI.ResultsAfter TBSI, there was significant diffuse axonal injury (DAI) in the brainstem of rats. A total of 579 genes, 70 proteins, and 183 metabolites showed significant changes in brainstem tissue. Through molecular function and pathway analysis, the differentially expressed genes, proteins, and metabolites of TBSI were mainly attributed to neural signal regulation, inflammation, neuroprotection, and immune system. In addition, a comprehensive analysis of transcripts, proteins, and metabolites showed that the genes, proteins, and metabolic pathways regulated in the brainstem after TBSI were involved in neuroactive ligand-receptor interaction. A variety of GCPR-regulated pathways were affected, especially GAGA’s corresponding receptors GABAA, GABAB, GABAC, and transporter GAT that were inhibited to varying degrees.ConclusionThis study provides insights into the development of a rapid diagnostic kit and making treatment strategies for TBSI.