缺血性卒中是严重影响人类生命健康的疾病, NMDAR介导的兴奋性毒性是神经元缺血损伤的关键环节，近年来的研究证明包含NR2A亚基的NMDAR主要在突触内介导细胞存活，包含NR2B亚基的NMDAR主要在突触外介导细胞死亡。咪唑啉化合物2-BFI是一种亲和力极高的咪唑啉I2受体的外源性配体，但是，我们在研究中首次发现2-BFI也是一种NMDAR拮抗剂，其抑制胞外Ca2+内流的方式与经典的抑制NMDA诱导的兴奋性毒性药物美金刚非常相似。 然而，2-BFI对NMDAR的抑制作用是否具有NMDAR亚基NR2A/NR2B的选择性还不清楚，本课题拟采用全细胞膜片钳技术观察2-BFI对N2A- NMDAR激活电流和N2B-NMDAR激活电流的影响，并通过OGD模型和MCAO模型观察2-BFI对N2A-NMDAR介导的促存活因子和N2B-NMDAR介导的促死亡因子的表达，为2-BFI 的临床转化提供理论依据

Ischemic stroke is a common cause of death and disability, The NMDA receptor mediated excitotoxicity is considered as main factor in the ischemia induced neuronal death. Recent studies have proved that NMDAR containing NR2A subunit is mainly located in the synapse mediates cell survival and the NMDAR containing NR2B subunit is mainly located in the extrasynapse mediates cell death. Imidazoline compound 2-BFI is a high affinity Imidazoline I2 receptor of exogenous ligand，but in our previous study we first found that 2-BFI is a NMDAR antagonist which inhibited extracellular Ca2+ influx in a manner similar to that of memantine, a Classic drugs for therapeutic inhibition NMDAR-induced excitotoxicity. Whether the inhibition of 2BFI on NMDAR has the selectivity for NR2A/NR2B subunit remain unclear. In this project, we will use the whole cell patch clamp to investigate the effect of 2-BFI on the N2A-NMDAR activated currents and the N2B-NMDAR activated currents , We will use OGD model and MCAO model to investigate the effect of 2-BFI on the expression of prosurvival factors mediated by N2A-NMDAR and the Pro death factor mediated by N2B-NMDAR. These research will provide a theoretical basis for the clinical transformation of 2-BFI.