Functional Analysis of the Cortical Transcriptome and Proteome Reveal Neurogenesis, Inflammation, and Cell Death after Repeated Traumatic Brain Injury In vivo

Abstract

The pathological effects of repeated traumatic brain injuries (TBIs) are largely unknown. To gain a detailed understanding of the cortical tissue acute biological response after one or two TBIs, we utilized RNA-sequencing and protein mass spectrometry techniques. Using our previously validated C57Bl/6 weight-drop model, we administered one or two TBIs of a mild or moderate severity. Double injury conditions were spaced 7 days apart, and cortical tissue was isolated 24?h after final injury. Analysis was carried out through functional gene annotation, utilizing Gene Ontology, for both the proteome and transcriptome. Major themes across the four different conditions include: neurogenesis; inflammation and immune response; cell death; angiogenesis; protein modification; and cell communication. Proteins associated with neurogenesis were found to be upregulated after single injuries. Transcripts associated with angiogenesis were upregulated in the moderate single, mild double, and moderate double TBI conditions. Genes associated with inflammation and immune response were upregulated in every condition, with the moderate single condition reporting the most functional groups. Proteins or genes involved in cell death, or apoptosis, were upregulated in every condition. Our results emphasize the significant differences found in proteomic and transcriptomic changes in single versus double injuries. Further, cortical omics analysis offers important insights for future studies aiming to deepen current knowledge on the development of secondary injuries and neurobehavioral impairments after brain trauma.

Keywords

• proteome
• repeated TBI
• TBI
• transcriptome