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

doi:10.1007/s11011-024-01426-4

. 2024 Nov 29;40(1):47.

doi: 10.1007/s11011-024-01426-4.

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

Lingman Wang^#¹, Jianxiong Gui^#¹, Ran Ding¹, Honghong Song¹, Bing Tian¹, Wandi Wang¹, Jie Liu¹, Li Jiang^{2

3}

Affiliations

¹ Department of Neurology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
² Department of Neurology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. dr_jiangcqmu@163.com.
³ Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, 40014, China. dr_jiangcqmu@163.com.

^# Contributed equally.

PMID: 39612062
DOI: 10.1007/s11011-024-01426-4

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

Lingman Wang et al. Metab Brain Dis. 2024.

. 2024 Nov 29;40(1):47.

doi: 10.1007/s11011-024-01426-4.

Authors

Lingman Wang^#¹, Jianxiong Gui^#¹, Ran Ding¹, Honghong Song¹, Bing Tian¹, Wandi Wang¹, Jie Liu¹, Li Jiang^{2

3}

Affiliations

¹ Department of Neurology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
² Department of Neurology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. dr_jiangcqmu@163.com.
³ Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, 40014, China. dr_jiangcqmu@163.com.

^# Contributed equally.

PMID: 39612062
DOI: 10.1007/s11011-024-01426-4

Abstract

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.

Keywords: Bioinformatics analysis; Epileptogenicity; Focal cortical dysplasia; Hub genes.

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Conflict of interest statement

Declarations. Competing interests: The authors have no relevant financial or non-financial interests to disclose.

References

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1. Aneja S, Jain P (2014) Refractory epilepsy in children. Indian J Pediatr 81:1063–1072. https://doi.org/10.1007/s12098-014-1533-1 - DOI - PubMed
1. Battaglia G, Colciaghi F, Finardi A, Nobili P (2013) Intrinsic epileptogenicity of dysplastic cortex: converging data from experimental models and human patients. Epilepsia 54(Suppl 6):33–36. https://doi.org/10.1111/epi.12272 - DOI - PubMed
1. Blumcke I, Thom M, Aronica E, Armstrong DD, Vinters HV, Palmini A, Jacques TS, Avanzini G, Barkovich AJ, Battaglia G, Becker A, Cepeda C, Cendes F, Colombo N, Crino P, Cross JH, Delalande O, Dubeau F, Duncan J, Guerrini R, Kahane P, Mathern G, Najm I, Ozkara C, Raybaud C, Represa A, Roper SN, Salamon N, Schulze-Bonhage A, Tassi L, Vezzani A, Spreafico R (2011) The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of the ILAE diagnostic methods commission. Epilepsia 52:158–174. https://doi.org/10.1111/j.1528-1167.2010.02777.x - DOI - PubMed

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[1] Ahmed Juvale II, Che Has AT (2020) The evolution of the pilocarpine animal model of status epilepticus. Heliyon 6:e04557. https://doi.org/10.1016/j.heliyon.2020.e04557 - DOI - PubMed - PMC

[2] Ahmed Juvale II, Che Has AT (2020) The evolution of the pilocarpine animal model of status epilepticus. Heliyon 6:e04557. https://doi.org/10.1016/j.heliyon.2020.e04557 - DOI - PubMed - PMC

[3] Andrioli A, Fabene PF, Mudo G, Barresi V, Di Liberto V, Frinchi M, Bentivoglio M, Condorelli DF (2022) Downregulation of the astroglial connexin expression and neurodegeneration after pilocarpine-induced status epilepticus. Int J Mol Sci 24. https://doi.org/10.3390/ijms24010023

[4] Andrioli A, Fabene PF, Mudo G, Barresi V, Di Liberto V, Frinchi M, Bentivoglio M, Condorelli DF (2022) Downregulation of the astroglial connexin expression and neurodegeneration after pilocarpine-induced status epilepticus. Int J Mol Sci 24. https://doi.org/10.3390/ijms24010023

[5] Aneja S, Jain P (2014) Refractory epilepsy in children. Indian J Pediatr 81:1063–1072. https://doi.org/10.1007/s12098-014-1533-1 - DOI - PubMed

[6] Aneja S, Jain P (2014) Refractory epilepsy in children. Indian J Pediatr 81:1063–1072. https://doi.org/10.1007/s12098-014-1533-1 - DOI - PubMed

[7] Battaglia G, Colciaghi F, Finardi A, Nobili P (2013) Intrinsic epileptogenicity of dysplastic cortex: converging data from experimental models and human patients. Epilepsia 54(Suppl 6):33–36. https://doi.org/10.1111/epi.12272 - DOI - PubMed

[8] Battaglia G, Colciaghi F, Finardi A, Nobili P (2013) Intrinsic epileptogenicity of dysplastic cortex: converging data from experimental models and human patients. Epilepsia 54(Suppl 6):33–36. https://doi.org/10.1111/epi.12272 - DOI - PubMed

[9] Blumcke I, Thom M, Aronica E, Armstrong DD, Vinters HV, Palmini A, Jacques TS, Avanzini G, Barkovich AJ, Battaglia G, Becker A, Cepeda C, Cendes F, Colombo N, Crino P, Cross JH, Delalande O, Dubeau F, Duncan J, Guerrini R, Kahane P, Mathern G, Najm I, Ozkara C, Raybaud C, Represa A, Roper SN, Salamon N, Schulze-Bonhage A, Tassi L, Vezzani A, Spreafico R (2011) The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of the ILAE diagnostic methods commission. Epilepsia 52:158–174. https://doi.org/10.1111/j.1528-1167.2010.02777.x - DOI - PubMed

[10] Blumcke I, Thom M, Aronica E, Armstrong DD, Vinters HV, Palmini A, Jacques TS, Avanzini G, Barkovich AJ, Battaglia G, Becker A, Cepeda C, Cendes F, Colombo N, Crino P, Cross JH, Delalande O, Dubeau F, Duncan J, Guerrini R, Kahane P, Mathern G, Najm I, Ozkara C, Raybaud C, Represa A, Roper SN, Salamon N, Schulze-Bonhage A, Tassi L, Vezzani A, Spreafico R (2011) The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of the ILAE diagnostic methods commission. Epilepsia 52:158–174. https://doi.org/10.1111/j.1528-1167.2010.02777.x - DOI - PubMed

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

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

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