Ravizza Teresa, Kostoula Chrysaugi, Vezzani Annamaria
Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Milano, Italy.
Neuropediatrics. 2013 Dec;44(6):330-5. doi: 10.1055/s-0033-1358601. Epub 2013 Oct 28.
The search of targets for developing novel drugs that can control seizures resistant to available treatments in children and adults represents a great challenge for basic science. In the past decade, emerging evidence pointed out to the crucial role played by glia, the innate immunity brain-resident cells, in the generation of hyperexcitable neuronal networks underlying seizures. Molecular and pharmacological studies targeting glia, and the inflammatory mediators released by these cells in experimental models of epilepsy, highlighted novel targets for drug intervention aimed at interfering with the disease mechanisms, therefore providing putative disease-modifying treatments. This article will focus on the role of immunity activation in the brain and the concomitant release by glia of inflammatory molecules with neuromodulatory properties, in the pathogenesis of epileptic seizures, cell loss, and comorbidities.
寻找能够控制儿童和成人中对现有治疗有抵抗性的癫痫发作的新型药物靶点,对基础科学而言是一项巨大挑战。在过去十年中,新出现的证据表明,神经胶质细胞(大脑中的固有免疫驻留细胞)在癫痫发作所依赖的过度兴奋神经网络的形成中发挥着关键作用。针对神经胶质细胞以及这些细胞在癫痫实验模型中释放的炎症介质进行的分子和药理学研究,突出了旨在干扰疾病机制的药物干预新靶点,从而提供了可能的疾病修饰治疗方法。本文将聚焦于大脑中免疫激活的作用以及神经胶质细胞同时释放具有神经调节特性的炎症分子在癫痫发作、细胞丢失和合并症发病机制中的作用。