文献类型： 外文期刊
作者： Fang, Chuantao 1 ; Zhang, Xiaodan 2 ; Yang, Lin 2 ; Sun, Licheng 1 ; Lu, Yujia 1 ; Liu, Yi 6 ; Guo, Jingjing 1 ; Wang, Min 2 ; Tan, Yanfeng 2 ; Zhang, Jinsen 2 ; Gao, Xin 7 ; Zhu, Li 8 ; Liu, Guoping 2 ; Ren, Maozhi 9 ; Xiao, Jianbo 6 ; Zhang, Fayong 2 ; Ma, Shaojie 10 ; Zhao, Rui 2 ; Mei, Xinyu 1 ; Qi, Dashi 1 ;
作者机构： 1.Tongji Univ, Yangpu Hosp, Sch Med, Ctr Clin Res & Translat Med, Shanghai, Peoples R China
2.Fudan Univ, Childrens Hosp, Huashan Hosp, Inst Pediat,Key Lab Med Neurobiol, Shanghai, Peoples R China
3.Fudan Univ, Obstet & Gynecol Hosp, Huashan Hosp, Inst Brain Sci,MOE Frontiers Ctr Brain Sci, Shanghai, Peoples R China
4.Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai, Peoples R China
5.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Inst Infect Dis & Vaccine Dev, Shanghai, Peoples R China
6.Univ Vigo, Inst Agroecoloxia Alimentac IAA CITEXVI, Dept Analyt Chem & Food Sci, Nutr & Bromatol Grp, Vigo, Spain
7.Shanghai Universal Med Imaging Diag Ctr, Shanghai, Peoples R China
8.Shanghai Jiao Tong Univ, Inst Translat Med, Shanghai, Peoples R China
9.Chinese Acad Agr Sci, Chengdu Natl Agr Sci & Technol Ctr, Inst Urban Agr, Chengdu, Peoples R China
10.Chinese Acad Sci, Univ Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Neurosci, Shanghai, Peoples R China
11.Childrens Hosp Shanghai, Dept Neurosurg, Shanghai, Peoples R China
12.Hainan Women & Childrens Med Ctr, Dept Neurosurg, Haikou, Peoples R China
期刊名称：NATURE COMMUNICATIONS （ 影响因子：15.7； 五年影响因子：17.2 ）
ISSN：
年卷期： 2025 年 16 卷 1 期
页码：
收录情况： SCI
摘要： Focal cortical dysplasia type II (FCDII) is a major cause of drug-resistant epilepsy, but genetic factors explain only some cases, suggesting other mechanisms. In this study, we conduct a molecular analysis of brain lesions and adjacent areas in FCDIIb patients. By analyzing over 217,506 single-nucleus transcriptional profiles from 15 individuals, we find significant changes in smooth muscle cells (SMCs) and astrocytes. We identify abnormal vascular malformations and a unique type of SMC that we call "Firework cells", which migrate from blood vessels into the brain parenchyma and associate with VIM+ cells. These abnormalities create localized ischemic-hypoxic (I/H) microenvironments, as confirmed by clinical data, further impairing astrocyte function, activating the HIF-1 alpha/mTOR/S6 pathway, and causing neuronal loss. Using zebrafish models, we demonstrate that vascular abnormalities resulting in I/H environments promote seizures. Our results highlight vascular malformations as a factor in FCDIIb pathogenesis, suggesting potential therapeutic avenues.
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