缺血性脑卒中是最常见致死致残性疾病，现有溶栓或取栓治疗除受治疗时间窗限制外，还不能避免治疗前缺血及治疗后再灌注所引起的脑组织损伤，因此尽早（甚至入院前）给予神经保护剂治疗是改善脑卒中患者预后的重要策略之一。我们发现，NMDA 受体辅助激动剂甘氨酸通过激活NMDA受体GluN2AR亚型的非离子通道活性对抗神经兴奋性毒性，甘氨酸还可通过上调miRNA-301a直接抑制PTEN表达发挥神经保护作用。预实验结果显示，甘氨酸可通过激活NMDA受体的非离子通道活性减少大鼠脑缺血损伤面积。因此我们假设：甘氨酸通过GluN2AR/miRNA-301a/PTEN信号通路发挥脑保护作用，我们将采用离体和在体脑缺血模型揭示甘氨酸如何通过这一信号通路发挥作用及其细胞和分子机制，研究结果为将甘氨酸研发成为一种新的脑保护候选药物提供重要的理论和实验依据。

Ischemia stroke is a severe disease with high morbidity and mortality. However, short time-window of thrombolytic therapy and thrombectomy limits clinical application. In addition, the thrombolytic therapy and thrombectomy do not protect against cerebral damage induced by ischemia-reperfusion. Thus, early application of neuroprotective drugs is a critical strategy to improve the prognosis of stroke patients. Our recent studies show that glycine, as the co-agonist of the NMDA receptor, triggers a non-ionotropic activity of GluN2AR to confer neuroprotection. We also show that glycine increases the expression of miRNA-301a that directly binds the 3'-UTR of PTEN to suppress PTEN expression and confer neuroprotection. Our recent unpublished data show that glycine treatment reduces the infarct volume of ischemic brain independent of the channel activity of NMDA receptors. Therefore, we hypothesize that GluN2AR/miRNA-301a/PTEN signal pathway mediates glycine-induced neuroprotection in ischemic stroke. In this study, we will investigate the mechanism of Glycine/GluN2AR/miRNA-301a/PTEN signal pathway in ischemia stroke in both in vitro and in vivo experimental models. The results from this study would provide critical experimental evidence for the development of glycine as a novel neuroprotection drug in ischemia stroke.