Identification and verification of key molecules in the epileptogenic process of focal cortical dysplasia.

Focal cortical dysplasia (FCD) represents a common developmental malformation associated with drug-resistant epilepsy (DRE) among children. However, the exact molecular mechanisms behind this condition are still unclear. In our study, FCD-associated microarray data from the Gene Expression Omnibus (GEO) database were analyzed. A comprehensive series of bioinformatics analyses were conducted, including screening for differentially expressed genes (DEGs), functional enrichment analysis, weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) analysis. Subsequently, a freezing lesion (FL) rat model was developed to validate expression levels of hub genes along with the molecular pathways behind FCD epileptogenicity. 320 DEGs were identified, and functional enrichment analysis revealed significant enrichment of these DEGs in "Neuroinflammatory response", "Cytokine production involved in immune response", and "Macrophage activation". Ultimately, 5 potential hub genes (CYBB, ITGAM, FCG3A, LY86, and CD86) were pinpointed. Notably, 4 hub genes (CYBB, ITGAM, FCG3A, and CD86) were validated in in vivo experiments, suggesting possible associations with neuroinflammation triggered by microglia. This underscores the tight relationship between microglia-induced neuroinflammation and the pathological progression of epileptic seizures in FCD. ITGAM, FCG3A, CD86, CYBB, and LY86 may emerge as promising candidate biomarkers, influencing diagnostic and therapeutic strategies.