促炎性因子（例如IL-1β）在癫痫发生发展的病理过程中发挥极重要作用。在前期工作中申请人发现晚期糖基化终末产物受体（RAGE）与其配体（如S100B）结合后可以刺激小胶质细胞大量表达IL-1β；同时我们还在难治性颞叶癫痫患者脑内发现RAGE和S100B呈现高度表达的现象。这些证据提示了RAGE/S100B axis可能参与了癫痫的发生发展过程。以此为基础，在本研究项目中我们一方面采用海人酸诱导的癫痫模型深入研究RAGE/S100B axis在癫痫发生中的作用和机制，以及使用RAGE诱饵受体（sRAGE）阻断这条通路的治疗效果；另一方面我们将使用细胞模型和颞叶癫痫病例深入研究RAGE基因 p.82G>S功能性突变对RAGE/S100B信号通路的放大功能以及该突变对癫痫活动和血清IL-1β表达的影响。本项研究不仅可以使我们对癫痫的发病机制有更深刻的理解，同时也可以为癫痫的治疗提供新的药物靶点。

Proinflammatory factors (such as IL-1β) play a prominent role in the etiology of epilepsy development. Our previous studies indicated that receptor for advanced glycation end products (RAGE) binding to its ligands (such as S100B) significantly stimulates the expression of IL-1β in microglia. Simultaneously, the expression of RAGE and S100B was found highly upregulated in the brain tissues of intractable temporal lobe epilepsy (TLE) patients. These lines of evidence suggest a role for the RAGE/S100B axis in developing of TLE. Based on above findings, the present study was aimed to further determine the role of RAGE/S100B axis in epileptogenesis using kainic acid-induced mice models, and the therapeutic effect exerted by blocking the RAGE/S100B signaling using the decoy receptor (sRAGE). In addition, we will further explore whether the RAGE p.82G>S functional mutation has an effect on RAGE/S100B signaling, epilepsy activity and serum IL-1β expression. The findings of this research will not only further our understanding on the pathogenesis of TLE, but also provide novel therapeutic targets for TLE treatment.