Vargas-Sánchez Karina, Mogilevskaya Maria, Rodríguez-Pérez John, Rubiano María G, Javela José J, González-Reyes Rodrigo E
Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia.
Universidad ECCI, Bogotá, Colombia.
Oncotarget. 2018 Jun 1;9(42):26954-26976. doi: 10.18632/oncotarget.25485.
Status epilepticus is a medical emergency with elevated morbidity and mortality rates, and represents a leading cause of epilepsy-related deaths. Though status epilepticus can occur at any age, it manifests more likely in children and elderly people. Despite the common prevalence of epileptic disorders, a complete explanation for the mechanisms leading to development of self-limited or long lasting seizures (as in status epilepticus) are still lacking. Apart from neurons, research evidence suggests the involvement of immune and glial cells in epileptogenesis. Among glial cells, astrocytes represent an ideal target for the study of the pathophysiology of status epilepticus, due to their key role in homeostatic balance of the central nervous system. During status epilepticus, astroglial cells are activated by the presence of cytokines, damage associated molecular patterns and reactive oxygen species. The persistent activation of astrocytes leads to a decrease in glutamate clearance with a corresponding accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Moreover, major alterations in astrocytic gap junction coupling, inflammation and receptor expression, facilitate the generation of seizures. Astrocytes are also involved in dysregulation of inhibitory transmission in the central nervous system and directly participate in ionic homeostatic alterations during status epilepticus. In the present review, we focus on the functional and structural changes in astrocytic activity that participate in the development and maintenance of status epilepticus, with special attention on concurrent inflammatory alterations. We also include potential astrocytic treatment targets for status epilepticus.
癫痫持续状态是一种发病率和死亡率均较高的医疗急症，是癫痫相关死亡的主要原因。尽管癫痫持续状态可发生于任何年龄，但在儿童和老年人中更为常见。尽管癫痫疾病普遍存在，但对于导致自限性或持续性发作（如癫痫持续状态）发展的机制仍缺乏完整解释。除神经元外，研究证据表明免疫细胞和神经胶质细胞也参与癫痫发生。在神经胶质细胞中，星形胶质细胞是研究癫痫持续状态病理生理学的理想靶点，因为它们在中枢神经系统的稳态平衡中起关键作用。在癫痫持续状态期间，星形胶质细胞会因细胞因子、损伤相关分子模式和活性氧的存在而被激活。星形胶质细胞的持续激活导致谷氨酸清除减少，相应地在突触细胞外空间积累，增加神经元兴奋性毒性的可能性。此外，星形胶质细胞间隙连接耦合、炎症和受体表达的主要改变促进了癫痫发作的产生。星形胶质细胞还参与中枢神经系统抑制性传递的失调，并在癫痫持续状态期间直接参与离子稳态改变。在本综述中，我们重点关注星形胶质细胞活动的功能和结构变化，这些变化参与癫痫持续状态的发生和维持，并特别关注并发的炎症改变。我们还包括癫痫持续状态潜在的星形胶质细胞治疗靶点。
