Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.
Nat Rev Neurol. 2022 Dec;18(12):707-722. doi: 10.1038/s41582-022-00727-5. Epub 2022 Oct 24.
Epilepsy affects ~65 million people worldwide. First-line treatment options include >20 antiseizure medications, but seizure control is not achieved in approximately one-third of patients. Antiseizure medications act primarily on neurons and can provide symptomatic control of seizures, but do not alter the onset and progression of epilepsy and can cause serious adverse effects. Therefore, medications with new cellular and molecular targets and mechanisms of action are needed. Accumulating evidence indicates that astrocytes are crucial to the pathophysiological mechanisms of epilepsy, raising the possibility that these cells could be novel therapeutic targets. In this Review, we discuss how dysregulation of key astrocyte functions - gliotransmission, cell metabolism and immune function - contribute to the development and progression of hyperexcitability in epilepsy. We consider strategies to mitigate astrocyte dysfunction in each of these areas, and provide an overview of how astrocyte activation states can be monitored in vivo not only to assess their contribution to disease but also to identify markers of disease processes and treatment effects. Improved understanding of the roles of astrocytes in epilepsy has the potential to lead to novel therapies to prevent the initiation and progression of epilepsy.
癫痫影响全球约 6500 万人。一线治疗选择包括 >20 种抗癫痫药物，但约三分之一的患者无法控制癫痫发作。抗癫痫药物主要作用于神经元，可以对癫痫发作进行症状控制，但不能改变癫痫的发作和进展，并可能导致严重的不良反应。因此，需要具有新的细胞和分子靶点以及作用机制的药物。越来越多的证据表明，星形胶质细胞对癫痫的病理生理机制至关重要，这增加了这些细胞可能成为新的治疗靶点的可能性。在这篇综述中，我们讨论了关键星形胶质细胞功能（神经递质传递、细胞代谢和免疫功能）的失调如何导致癫痫过度兴奋的发展和进展。我们考虑了在这些领域减轻星形胶质细胞功能障碍的策略，并概述了如何在体内监测星形胶质细胞激活状态，不仅可以评估其对疾病的贡献，还可以识别疾病过程和治疗效果的标志物。对星形胶质细胞在癫痫中的作用的更好理解有可能导致预防癫痫发作和进展的新疗法。
