Badanie mechanizmów powstawania epilepsji pourazowej na podstawie analizy bioinformatycznej
Exploring the pathogenesis of traumatic brain injury and traumatic epilepsy based on bioinformatics analysis
W skrócie
[Preprint - wstępne wyniki] Naukowcy przeanalizowali dane genetyczne pacjentów z urazami głowy i epilepsją pourazową, aby znaleźć wspólne zmutowane geny odpowiadające za te schorzenia. Odkryli, że geny DUSP1 i EGR1 są kluczowym połączeniem między urazem głowy a rozwojem epilepsji, co potwierdzono także w doświadczeniach na myszach. Wyniki sugerują, że te geny mogą być nowymi celami do leczenia epilepsji pourazowej i zapobiegania jej rozwojowi.
Oryginalny abstract (angielski)
Abstract Background :Traumatic brain injury (TBI) is a well-established risk factor for the development of post-traumatic epilepsy (PTE). However, the molecular mechanisms linking TBI to PTE remain incompletely understood. This study aimed to explore the shared molecular signatures and underlying pathogenic mechanisms between TBI and PTE, thereby providing novel insights into the prevention and treatment of PTE. Materials and Methods :Publicly available transcriptomic datasets from patients with TBI and PTE were analyzed to identify common differentially expressed genes (DEGs). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to elucidate the biological functions and signaling pathways associated with the shared DEGs. Protein–protein interaction (PPI) networks were subsequently constructed to identify key hub genes. Candidate hub genes were further validated using the Comparative Toxicogenomics Database (CTD). In addition, the expression levels of the identified core genes were experimentally validated in a controlled cortical impact (CCI)-induced mouse model of TBI. Results :Integrated bioinformatics analyses revealed significant transcriptomic similarities between TBI and PTE, highlighting shared molecular pathways and regulatory networks involved in disease progression. Among the identified hub genes, DUSP1 and EGR1 emerged as pivotal regulators, exhibiting significant differential expression across both TBI and PTE datasets. Experimental validation in the CCI-induced TBI mouse model further confirmed the dysregulated expression of these genes. Conclusion :Our findings demonstrate that DUSP1 and EGR1 represent key molecular links between TBI and PTE and may serve as promising therapeutic targets for the prevention and treatment of TBI-associated PTE. These results enhance our understanding of the molecular mechanisms underlying epileptogenesis following TBI and provide a foundation for the development of novel targeted therapeutic strategies.