Guiding Epilepsy Surgery by Intraoperatively Visualizing Proinflammatory Microglia via a Ratiometric Surface-Enhanced Raman Scattering Nanosensor

Abstract Resective surgery is used for long-term seizure control in drug-resistant focal epilepsy when the epileptic focus (EF) can be accurately delineated and removed. However, as the “gold standard” technique for mapping EF intraoperatively, electroencephalography is laborious, time-consuming and highly vulnerable to anaesthesia. Here, we demonstrated hypochlorous acid (HOCl), a bioproduct of activated proinflammatory microglia, can be reliable biomarkers for EF localization. With a newly developed HOCI ratiometric Raman nanosensor, ultraHOCls, we can accurately locate EF in live kainic-acid-induced mice by visualizing proinflammatory microglia ignoring the interference of anaesthesia. Moreover, ultraHOCls provided a 1-hour stable imaging time-window for locating EF, which is more than 100 times longer than single neuroelectric activity recorded by electroencephalography. UltraHOCls-guided surgery showed a 72% reduction in total seizure time in mice in comparison to electroencephalography-guided surgery. This work provides an alternative strategy for locating EF intraoperatively and holds promise in improving surgical outcomes in epilepsy patients.