Li Gen, Tian Ye, Jiang Luyue, Jin Shuang, Ye Yifei, Lu Yunxiao, Su Haoyang, Yang Yingkang, Wei Xiaoling, Zhou Zhitao, Tao Tiger H, Sun Liuyang
2020 X-Lab, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China; State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; School of Graduate Study, University of Chinese Academy of Sciences, Beijing, 100049, China.
2020 X-Lab, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
Biosens Bioelectron. 2025 Mar 1;271:117071. doi: 10.1016/j.bios.2024.117071. Epub 2024 Dec 16.
Anti-seizure medications and deep brain stimulation are widely used therapies to treat seizures; however, both face limitations such as resistance and the unpredictable nature of seizures. Recent advancements, including responsive neural stimulation and on-demand drug release, have been developed to address these challenges. However, a gap remains, as electrical stimulation provides only transient effects while medication has a delayed onset. To bridge this gap, we developed a Bimodal Closed-loop Neurostimulation Implant System that integrates real-time neural recording, immediate electrical stimulation, and on-demand drug release to achieve more effective seizure suppression. This dual-modality system combines rapid electrical intervention with sustained pharmacological treatment to provide comprehensive seizure control. An embedded platform powered by a Long Short-Term Memory network detects seizures and autonomously triggers these interventions. In vivo studies in an epileptic mouse model revealed that electrical stimulation achieved rapid seizure suppression, terminating 75.16% of seizures, with 90% of episodes suppressed within 10 s. The subcutaneous drug capsule provided additional control, with an onset of action approximately 15 min after release. The dual-modality approach bridged the gap between immediate and delayed intervention, stabilizing neural activity and reducing seizure recurrence. Furthermore, we confirmed the long-term viability of neurons, observing no significant changes in morphology or signal quality following stimulation and drug release. These results suggest that the system offers rapid, stable, and minimally invasive seizure control, making it a promising therapeutic tool for epilepsy. By bridging the gap between electrical effects and delayed pharmacological action, the system presents a novel approach to epilepsy management.
抗癫痫药物和深部脑刺激是治疗癫痫的广泛应用的疗法；然而，两者都面临诸如耐药性和癫痫发作不可预测性等局限性。最近已经开发出包括响应性神经刺激和按需药物释放在内的进展来应对这些挑战。然而，差距仍然存在，因为电刺激仅提供短暂效果，而药物治疗起效延迟。为了弥合这一差距，我们开发了一种双模式闭环神经刺激植入系统，该系统集成了实时神经记录、即时电刺激和按需药物释放，以实现更有效的癫痫发作抑制。这种双模式系统将快速电干预与持续药物治疗相结合，以提供全面的癫痫发作控制。一个由长短期记忆网络驱动的嵌入式平台检测癫痫发作并自主触发这些干预措施。在癫痫小鼠模型中的体内研究表明，电刺激实现了快速的癫痫发作抑制，终止了75.16%的癫痫发作，90%的发作在10秒内得到抑制。皮下药物胶囊提供了额外的控制，释放后约15分钟起效。这种双模式方法弥合了即时干预和延迟干预之间的差距，稳定了神经活动并减少了癫痫复发。此外，我们证实了神经元的长期活力，在刺激和药物释放后未观察到形态或信号质量的显著变化。这些结果表明，该系统提供了快速、稳定且微创的癫痫发作控制，使其成为一种有前途的癫痫治疗工具。通过弥合电效应和延迟药理作用之间的差距，该系统提出了一种新颖的癫痫管理方法。
