biostudies-literatureUnknown6(6)Wang CShanghai Municipal Health CommissionNational Science Fund for Distinguished Young ScholarsNational Natural Science Foundation of ChinaNational Postdoctoral Program for Innovative TalentsResective 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 moCell reports. Medicine102155https://www.ebi.ac.uk/biostudies/studies/S-EPMC12208331biostudies-literatureUltrabright ratiometric Raman-guided epilepsy surgery by intraoperatively visualizing proinflammatory microglia.PMC12208331Zhang JWang CWang DWang JWang LJiang YDing YXie FZheng HWang QChen YZhao JZheng FMao YYan KLi CFan ZChen MChen LXiao XSun WZhou XGuan YLi ZLei ZHu JCai ZZhu XDuan WfalseUltrabright 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 mo2025-01-01T00:00:00Z2025 Jun2026-06-01T16:01:47.528Z2026-04-08T14:04:23.756ZS-EPMC122083314044948210.1016/j.xcrm.2025.102155