以往一直认为缺血性脑损伤（IBI）后兴奋性氨基酸毒性、Ca2+超载和自由基释放等导致神经元死亡，其中细胞凋亡发挥重要作用，但根据这些理论设计的治疗方法在临床应用并无佳效。可能未充分考虑到神经元死亡还可通过另一方式，过度"自噬"的作用。我们前期研究发现，IBI后，大量神经元凋亡和自噬；②干涉神经元Notch信号，可抑制Homer1a表达，自噬相关分子Akt、Beclin1、LC3等表达变化，加重神经元死亡。这些结果提示，Notch信号与Homer在IBI中相互作用，通过调控自噬和凋亡相关分子影响神经元转归，但两者具体作用关系和分子调控机制不清。本课题在上述工作基础上，利用神经元剔除RBP-J和Homer1a基因小鼠，深入探讨IBI后Notch和Homer1a的具体作用关系，剖析两者关系对神经元转归，特别是自噬的影响，揭示两者影响自噬的具体分子调控网络，为临床治疗IBI与神经变性疾病提供新手段

Excitotoxicty of glutamate, Ca2+ overloading and free radical release and so on have long been considered to cause neurons death, especially neurons apoptosis plays a very important role in ischemic brain injury. However, treatment methods designed according to these theories are not effective in clinical application. The reason is because the effect of autophagy, which is another way of cell death，is not considered fully. Our previous studies showed that there were a lot of apoptosis and neurons autophagy after ischemic brain injury; down-regulating neuronal Notch signal may not only suppress Homerla expression, but also regulate Akt、Beclin 1 and LC3 and so on which are autophagy related molecular, and increase neuronal death as a result. It is suggested that the interaction between Notch signal and Homer may have effects on the prognosis of neurons by regulating autophagy and apoptosis related molecular after ischemic brain injury. However, it is unclear how Notch signal and Homer works on the prognosis and what molecular signal transduction mechanism may be involved in ischemic brain injury. Based on the previous results, by specific RBP-J and Homer1a knockout mices, we shanll study deeply the interaction between Notch siganl and Homer1a associate with ischemic brain injury, and analyzes the effects of this interaction on the outcome of neurons, especially for autophagy. In order to illustrates the molecular regulating mechanism. It may form therotical basis for new treatment to effectively alleviate ischemic brain injury and decrease morbidity and mortality.