通过术中可视化促炎小胶质细胞实现超亮比率拉曼引导的癫痫手术
Ultrabright ratiometric Raman-guided epilepsy surgery by intraoperatively visualizing proinflammatory microglia.
作者信息
Wang Cong, Li Zhi, Zhu Xiao, Sun Wanbing, Ding Yue, Duan Wenjia, Wang Difei, Jiang Yiqing, Chen Ming, Chen Yuncan, Hu Jiayi, Cai Zheping, Zhao Jing, Wang Junfeng, Fan Zhen, Zheng Faming, Zhou Xingyu, Xie Fang, Zhang Jianping, Guan Yihui, Yan Kui, Lei Zuhai, Wang Qinyue, Wang Luting, Xiao Xiao, Zheng Hairong, Chen Liang, Li Cong, Mao Ying
机构信息
MOE Key Laboratory of Smart Drug Delivery, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, School of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China; Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China; The Key Laboratory of Biomedical Imaging Science and System, Chinese Academy of Sciences, State Key Laboratory of Biomedical Imaging Science and System, Shenzhen 518055, China.
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China; Department of Neurosurgery/Neuro-oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
出版信息
Cell Rep Med. 2025 Jun 17;6(6):102155. doi: 10.1016/j.xcrm.2025.102155. Epub 2025 May 30.
Resective surgery is an effective approach for long-term seizure control in drug-resistant focal epilepsy when the epileptic focus (EF) can be accurately delineated and removed. However, intraoperative mapping of EF with electrocorticography is laborious, time-consuming, and highly vulnerable to the effects of anesthesia. Here, we demonstrated that activated microglia can be reliable biomarkers for EF localization. Leveraging a newly developed ratiometric Raman nanosensor, ultraHOCls, we successfully visualize proinflammatory microglia in live epileptic mice, allowing for precise EF delineation without the interference of anesthesia. Compared to electrocorticography-guided surgery, ultraHOCl-guided surgery results in a substantial 61% reduction in total seizure burden in epileptic mouse models. Notably, ultraHOCls sprayed on freshly excised human brain tissues can effectively discriminate epileptic regions from non-epileptic tissues with high sensitivity (94.89%) and specificity (93.3%). This work provides an alternative strategy for delineating the EF intraoperatively, potentially revolutionizing surgery outcomes in epilepsy patients.
对于药物难治性局灶性癫痫，当癫痫病灶（EF）能够被准确界定并切除时，切除性手术是实现长期癫痫控制的有效方法。然而，术中通过皮质脑电图对EF进行定位既费力又耗时，而且极易受到麻醉效果的影响。在此，我们证明活化的小胶质细胞可以作为EF定位的可靠生物标志物。利用新开发的比率型拉曼纳米传感器ultraHOCls，我们成功地在活体癫痫小鼠中可视化促炎性小胶质细胞，从而在无麻醉干扰的情况下精确界定EF。与皮质脑电图引导的手术相比，ultraHOCl引导的手术在癫痫小鼠模型中使总癫痫负担大幅降低了61%。值得注意的是，喷洒在新鲜切除的人脑组织上的ultraHOCls能够以高灵敏度（94.89%）和特异性（93.3%）有效区分癫痫区域和非癫痫组织。这项工作为术中界定EF提供了一种替代策略，有望彻底改变癫痫患者的手术治疗效果。
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