Ultrabright ratiometric Raman-guided epilepsy surgery by intraoperatively visualizing proinflammatory microglia
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.
Authors
- Qinyue Wang
- Zuhai Lei (ORCID: https://orcid.org/0000-0001-6851-6044)
- Hairong Zheng (ORCID: https://orcid.org/0000-0002-8558-5102)
- Yuncan Chen
- Xiao Zhu (ORCID: https://orcid.org/0000-0003-3295-619X)
- Fang Xie (ORCID: https://orcid.org/0000-0002-2177-2283)
- Yiqing Jiang
- Wenjia Duan (ORCID: https://orcid.org/0000-0002-9264-625X)
- Kui Yan
- Jiayi Hu (ORCID: https://orcid.org/0009-0008-0103-1200)
- Zheping Cai
- Cong Li (ORCID: https://orcid.org/0000-0001-7731-8031)
- Liang Chen (ORCID: https://orcid.org/0000-0002-2373-5363)
- Zhi Li (ORCID: https://orcid.org/0000-0002-7563-9998)
- Jianping Zhang (ORCID: https://orcid.org/0000-0002-9216-2386)
- Cong Wang (ORCID: https://orcid.org/0000-0002-2236-4636)
- Ming Chen (ORCID: https://orcid.org/0000-0001-5041-9342)
- Xiao Xiao (ORCID: https://orcid.org/0000-0002-4328-0634)
- Faming Zheng
- Junfeng Wang (ORCID: https://orcid.org/0009-0007-4494-2170)
- Jing Zhao (ORCID: https://orcid.org/0000-0002-1980-280X)
- Yue Ding (ORCID: https://orcid.org/0000-0003-3662-8265)
- Yihui Guan (ORCID: https://orcid.org/0000-0002-2946-4293)
- Zhen Fan (ORCID: https://orcid.org/0000-0002-7771-2378)
- Xingyu Zhou (ORCID: https://orcid.org/0000-0003-3301-9106)
- Luting Wang (ORCID: https://orcid.org/0009-0006-3294-7006)
- Difei Wang (ORCID: https://orcid.org/0000-0002-5581-9094)
- Wanbing Sun
- Ying Mao (ORCID: https://orcid.org/0000-0001-8055-115X)
Institutions
- Sun Yat-sen University (CN)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Vanderbilt University (US)
- Fudan University (CN)
- Shanghai Mental Health Center (CN)
- State Key Laboratory of Transducer Technology (CN)
- King's College Hospital NHS Foundation Trust (GB)
- Shanghai Institute of Materia Medica (CN)
- Institute of Forensic Science (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- Sun Yat-sen University Cancer Center (CN)
- Shanghai Institute of Microsystem and Information Technology (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Huashan Hospital (CN)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-05-30
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102155
- Citations
- 2
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.68
Funders
- Shanghai Municipal Health Commission
- National Natural Science Foundation of China
- National Postdoctoral Program for Innovative Talents
- National Science Fund for Distinguished Young Scholars