BBB proteomic analysis reveals that complex febrile seizures in infancy enhance susceptibility to epilepsy in adulthood through dysregulation of ECM-receptor interaction signaling pathway

作者：Qian Wang, Liangyu Pan, Siruan Chen, Yuyu Zhang, Guangyuan Liu, Yiying Wu, Xia Qin, Panpan Zhang, Wei Zhang, Jianghua Zhang, Dezhi Kong · 发表于：Fluids and Barriers of the CNS · 年份：2025 · DOI：10.1186/s12987-025-00660-x · 被引用次数：8 · 研究领域：Epilepsy research and treatment、Barrier Structure and Function Studies、Neuroscience and Neuropharmacology Research

BACKGROUND: Complex febrile seizures (CFS) have been associated with an increased risk of epilepsy in adulthood. However, the specific link between blood-brain barrier (BBB) and the predisposition to epilepsy in adults who experienced CFS during infancy remains unclear. The objective of this study was to investigate the alteration of BBB in adult mice who had experienced CFS during infancy, and to explore the mechanisms of increased susceptibility to epilepsy after CFS. METHODS: The CFS pup model was induced using hot air, and the seizure susceptibility was examined using low-dose pentylenetetrazole (PTZ) after 8 W. The brain microvessels representing BBB function were isolated and their protein expression changes were analyzed using data-independent acquisition (DIA) proteomic techniques. Subsequently, the bioinformatic analyses were performed using ClusterProfiler, STRING, Gene Set Enrichment Analysis (GSEA), etc. The enriched pathways, changes in the expression of BBB-related proteins, and alterations in metabolites including certain neurotransmitters were subsequently validated by Western Blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and mass spectrometric imaging (MSI). In addition, we selected the MMP inhibitor Incyclinide to verify that dysregulation of the ECM-receptor interaction signaling pathway increases epilepsy susceptibility in adult mice. RESULTS: Mice that experienced CFS in infancy show increased susceptibility to epilepsy in adulthoo...