Analysis of Post-Traumatic Brain Injury Gene Expression Signature Reveals Tubulins, Nfe2l2, Nfkb, Cd44, and S100a4 as Treatment Targets
| Autor: | Jussi Paananen, Asla Pitkänen, Anssi Lipponen, Noora Puhakka |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Traumatic brain injury NF-E2-Related Factor 2 Gene regulatory network Gene Expression Biology Bioinformatics Epileptogenesis Article Transcriptome 03 medical and health sciences 0302 clinical medicine Tubulin Gene expression Brain Injuries Traumatic medicine Humans Gene Regulatory Networks S100 Calcium-Binding Protein A4 Gene TUBB3 Multidisciplinary Epilepsy NF-kappa B Brain medicine.disease NFE2L2 3. Good health 030104 developmental biology Hyaluronan Receptors 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | We aimed to define the chronically altered gene expression signature of traumatic brain injury (TBI-sig) to discover novel treatments to reverse pathologic gene expression or reinforce the expression of recovery-related genes. Genome-wide RNA-sequencing was performed at 3 months post-TBI induced by lateral fluid-percussion injury in rats. We found 4964 regulated genes in the perilesional cortex and 1966 in the thalamus (FDR in vivo animal models of epilepsy. Other compounds revealed by the analysis were BRD-K91844626, BRD-A11009626, NO-ASA, BRD-K55260239, SDZ-NKT-343, STK-661558, BRD-K75971499, ionomycin and desmethylclomipramine. Network analysis of overlapping genes revealed the effects on tubulins (Tubb2a, Tubb3, Tubb4b), Nfe2l2, S100a4, Cd44 and Nfkb2, all of which are linked to TBI-relevant outcomes, including epileptogenesis and tissue repair. Desmethylclomipramine modulated most of the gene targets considered favorable for TBI outcome. Our data demonstrate long-lasting transcriptomics changes after TBI. LINCS analysis predicted that these changes could be modulated by various compounds, some of which are already in clinical use but never tested in TBI. |
| Databáze: | OpenAIRE |
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