Negative regulation of angiogenesis and the MAPK pathway may be a shared biological pathway between IS and epilepsy

PLoS One. 2023 Oct 4;18(10):e0286426. doi: 10.1371/journal.pone.0286426. eCollection 2023.

Abstract

Ischemia stroke and epilepsy are two neurological diseases that have significant patient and societal burden, with similar symptoms of neurological deficits. However, the underlying mechanism of their co-morbidity are still unclear. In this study, we performed a combined analysis of six gene expression profiles (GSE58294, GSE22255, GSE143272, GSE88723, GSE163654, and GSE174574) to reveal the common mechanisms of IS and epilepsy. In the mouse datasets, 74 genes were co-upregulated and 7 genes were co-downregulated in the stroke and epilepsy groups. Further analysis revealed that the co-expressed differentially expressed genes (DEGs) were involved in negative regulation of angiogenesis and the MAPK signaling pathway, and this was verified by Gene Set Enrichment Analysis of human datasets and single cell RNA sequence of middle cerebral artery occlusion mice. In addition, combining DEGs of human and mouse, PTGS2, TMCC3, KCNJ2, and GADD45B were identified as cross species conserved hub genes. Meanwhile, molecular docking results revealed that trichostatin A and valproic acid may be potential therapeutic drugs. In conclusion, to our best knowledge, this study conducted the first comorbidity analysis of epilepsy and ischemic stroke to identify the potential common pathogenic mechanisms and drugs. The findings may provide an important reference for the further studies on post-stroke epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epilepsy* / genetics
  • Gene Expression Profiling / methods
  • Humans
  • Mice
  • Molecular Docking Simulation
  • Stroke* / genetics
  • Stroke* / metabolism
  • Transcriptome

Grants and funding

This work was supported by Xi 'an Science and Technology Plan (21YXYJ0116), the Key Research And Development Project of Shaanxi Province (Grant No.2022ZDLSF04-01, and No.2019KW-071), The National Natural Science Foundation of China (Grant No. 81971766, and Grant No. 81903268), and China Postdoctoral Science Foundation (No.2021M692577). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.