Ghouli Manolia R, Binder Devin K
Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, United States; Center for Glial-Neuronal Interactions, University of California, Riverside, Riverside, CA, United States.
Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, United States; Center for Glial-Neuronal Interactions, University of California, Riverside, Riverside, CA, United States.
Handb Clin Neurol. 2025;210:69-86. doi: 10.1016/B978-0-443-19102-2.00016-8.
Epilepsy is a group of neurologic diseases characterized by spontaneous, repetitive disruption to neuronal activity. Neurons have been at the core of epilepsy research efforts, and pharmacotherapies historically have been generated by targeting neuronal mechanisms. As a result, most currently available antiseizure drugs (ASDs) work to either decrease excitatory glutamatergic neurotransmission or to increase inhibitory GABAergic neurotransmission. However, ASDs may have undesirable side effects on cognition and also fail to control seizures in approximately 30% of epilepsy patients. In recent years, glia have surfaced as essential modulators of neuronal function in health and disease. The redirection of focus onto neuroglia provides new perspectives and opportunities to generate novel therapeutic targets that may treat refractory epilepsy and diminish the unwanted side effect profile of current treatments. In this chapter, we discuss the contribution of astroglia, oligodendroglia, and microglia to the genesis, development, and progression of epilepsy, and we highlight key enzymes, receptors, transporters, and channels that may be pursued as nonneuronal targets for novel ASDs.
癫痫是一组以神经元活动自发、重复性紊乱为特征的神经系统疾病。神经元一直是癫痫研究工作的核心，从历史上看，药物治疗一直是通过针对神经元机制来产生的。因此，目前大多数可用的抗癫痫药物（ASD）要么致力于减少兴奋性谷氨酸能神经传递，要么致力于增加抑制性γ-氨基丁酸能神经传递。然而，ASD可能对认知有不良副作用，并且在大约30%的癫痫患者中无法控制癫痫发作。近年来，神经胶质细胞已成为健康和疾病中神经元功能的重要调节因子。将研究重点转向神经胶质细胞为产生新的治疗靶点提供了新的视角和机会，这些靶点可能治疗难治性癫痫并减少当前治疗的不良副作用。在本章中，我们讨论星形胶质细胞、少突胶质细胞和小胶质细胞对癫痫的发生、发展和进展的作用，并强调可能作为新型ASD非神经元靶点的关键酶、受体、转运体和通道。
