GDNF预处理递载丛蛋白Plexin B2细胞外囊泡在缺血性脑卒中神经损伤中的机制研究

随着医疗条件的进步，卒中患者的死亡率逐渐降低，但幸存患者的预后较差。脑缺血后神经元损伤的程度是决定预后的主要因素。因此，需要进一步阐明拯救受损神经元的调控机制，以寻求有效降低神经元损伤的治疗方案。申请人预实验发现，脑缺血周围区皮层中Plexin B2表达下调，Plexin B2下调显著加重脑梗死体积，Plexin B2主要表达在神经元细胞中。构建靶向中枢的GDNF预处理递载Plexin B2细胞外囊泡（GDNF-Plexin B2-EVs）确认其能靶向到脑部及促进脑卒中后功能恢复。基于此，申请人提出“GDNF预处理递载丛蛋白Plexin B2细胞外囊泡促进缺血性脑卒中后的神经损伤修复”这一科学假设。本项目将从动物、细胞和分子水平，深入探讨GDNF-Plexin B2-Evs对缺血性脑卒中后神经损伤修复的作用,明确Plexin B2在神经元凋亡中的分子机制，为促进脑卒中神经损伤修复提供靶标。

With the advancement of medical conditions, the mortality of stroke patients has gradually decreased, but the prognosis of surviving patients is poor. The degree of neuronal damage after cerebral ischemia is the main factor determining the prognosis. Therefore, it is necessary to further clarify the regulatory mechanism of saving damaged neurons to seek effective treatments. The applicants previous studies found that the expression of Plexin B2 in the peri-infarct cortex was down-regulated, and the down-regulation of Plexin B2 significantly increased cerebral infarction volume. Moreover, the Plexin B2 was mainly expressed in neurons. Based on previous studies, the applicant constructed GDNF-pretreated Plexin B2 extracellular vesicles (GDNF-Plexin B2-EVs) and confirmed that these EVs could target the brain and promote functional recovery after stroke. Based on these findings, the applicant proposed the scientific hypothesis of “ The GDNF-pretreated extracellular vesicles containing Plexin B2 promte nerve injury after ischemic stroke”. This project aims to explore the effect of GDNF-Plexin B2-EVs on the repair of nerve damage after ischemic stroke from the animal, cell and molecular level, clarify the role and molecular mechanism of Plexin B2 in neuronal apoptosis and provide a target for promoting the repair of nerve injury in stroke.