中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (1): 23-38.doi: 10.4103/NRR.NRR-D-24-01035

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

超越神经元的癫痫治疗：揭秘作为细胞靶点的星形胶质细胞

  

  • 出版日期:2026-01-15 发布日期:2025-04-18
  • 基金资助:
    本研究得到国家重点研发计划项目 2023YFF0714200、国家自然科学基金项目 82472038 和 82202224、上海市科技新星计划项目 23QA1407700、国家自然科学基金委，编号：82472038 和 82202224；上海市科技新星计划，编号：23QA1407700；上海市分子影像重点实验室建设项目，编号：18QA1407700。 上海市分子影像重点实验室建设项目，编号：18DZ2260400；国家杰出青年科学基金，编号：82025019。 82025019；粤港澳大湾区精准医学研究院（广州）。

Epilepsy therapy beyond neurons: Unveiling astrocytes as cellular targets

Yuncan Chen1, #, Jiayi Hu1, #, Ying Zhang2 , Lulu Peng1 , Xiaoyu Li2 , Cong Li1, 3, *, Xunyi Wu1, *, Cong Wang1, 3, 4, 5, *   

  1. 1 Shanghai Fifth People’s Hospital, School of Pharmacy, MOE Key Laboratory of Smart Drug Delivery, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China;  2 Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China;  3 Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, China;  4 Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Shanghai, China;  5 Key Laboratory of Biomedical Imaging Science and System, Chinese Academy of Sciences, Shenzhen, Guangdong Province, China
  • Online:2026-01-15 Published:2025-04-18
  • Contact: Cong Wang, PhD, cong_wang@fudan.edu.cn; Xunyi Wu, PhD, dr.xunyiwu@163.com; Cong Li, PhD, congli@fudan.edu.cn.
  • Supported by:
    This work was supported by the National Key Research and Development Program of China, No. 2023YFF0714200 (to CW); the National Natural Science Foundation of China, Nos. 82472038 and 82202224 (both to CW); the Shanghai Rising-Star Program, No. 23QA1407700 (to CW); the Construction Project of Shanghai Key Laboratory of Molecular Imaging, No. 18DZ2260400 (to CW); the National Science Foundation for Distinguished Young Scholars, No. 82025019 (to CL); and the Greater Bay Area Institute of Precision Medicine (Guangzhou) (to CW).

PDF

23

摘要：

癫痫是全球致残和致死的主要原因之一；然而，尽管有 20 多种抗癫痫药物可用，但仍有1/3以上的患者继续经历癫痫发作。由于迫切需要探索新的癫痫治疗策略，已经有一些新的癫痫治疗研究突显了操纵神经胶质增生、代谢紊乱和神经回路异常的潜力。星形胶质细胞作为中枢神经系统内数量最为庞大的非神经元细胞群体，扮演着维持神经元离子与能量代谢稳态、调节神经递质水平及突触可塑性等多重关键角色。为此，文章简要回顾了星形胶质细胞在维持中枢神经系统平衡中的重要作用。文章在以往研究的基础上，讨论了星形胶质细胞的功能障碍是如何通过兴奋性和抑制性神经元信号传导失衡、神经元微环境代谢平衡失调、神经炎症和异常神经回路的形成这4个方面导致癫痫的发生和发展情况。文章总结了以往5年来围绕调节星形胶质细胞作为癫痫治疗手段所开展的相关基础研究进展，并将这些研究提出的治疗目标分为4个方面：恢复兴奋-抑制平衡、重建代谢平衡、调节免疫和炎症平衡以及重建异常神经回路，与星形胶质细胞促发癫痫的病理生理机制相对应。此外，还需要考虑到将已确定的治疗靶点转化为临床治疗的潜在挑战和局限性，这些局限性源于人类与动物模型之间的种间差异，以及人类癫痫的复合合并症。在癫痫治疗和星形胶质细胞调控方面有一些值得探索的有价值的未来研究方向，如星形胶质细胞的基因治疗和成像策略。文章结果有助于为耐药性癫痫患者和其他与星形胶质细胞功能障碍相关的中枢神经系统疾病患者开辟新的治疗途径。

https://orcid.org/0000-0002-2236-4636 (Cong Wang); https://orcid.org/0000-0002-7006-4419 (Xunyi Wu);

https://orcid.org/0000-0001-7731-8031 (Cong Li)

关键词: 星形胶质细胞, 细胞微环境, 耐药性, 癫痫, 兴奋性, 平衡, 新陈代谢, 神经网络, 神经炎症, 神经元

Abstract: Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.

Key words: astrocyte, cellular microenvironment, drug resistance, epilepsy, excitability, homeostasis, metabolism, neural networks, neuroinflammation, neuron