新生儿缺氧缺血性脑病（HIE）是围产期最常见的中枢神经系统疾病，主要表现为预后运动和认知功能障碍，这些伤残儿童给社会和家庭带来沉重的物质和精神负担。然而，目前还没有一种有效的方法能够治愈这类神经系统疾病。虽然阻断NMDA受体可以缓解HIE症状，但同时也损伤正常的突触传递和学习记忆等功能。因此，通过阻断NMDA受体来治疗HIE是不科学的。本项目拟从NMDA受体下游信号分子抑癌蛋白PTEN入手，在新生大鼠缺氧缺血性脑损伤（HIBD）模型上，通过应用人工合成多肽Tat-K13抑制PTEN核转移，然后通过多种行为学和电生理方法对HIBD大鼠的运动和认知功能进行检测，以揭示抑制PTEN核转移在HIBD治疗中的作用。并在原代培养神经元上，进一步探索缺血缺氧对PTEN单泛素化的影响，以及Nedd4-1在其中的作用，揭示缺血缺氧诱导PTEN核转移的分子机理，为临床治疗HIE提供新的靶点和方法。

Hypoxic-ischemic encephalopathy (HIE) is the most common perinatal diseases of the central nervous system, which is characterized by motor and cognitive impairments. HIE causes significant burden and distress on the affected families and the society, but no effective cure yet exists. Although the blockade of NMDA receptors could relieve the symptoms of HIE, it is not a good candidate for treatment, because it also affects the normal synaptic transmission and consequently the learning and memory. Thus, the treatment of HIE by simply blocking the NMDA receptors is not practical. This study aims at revealing the roles of NMDA receptor downstream signaling molecules, such as tumor suppressor protein PTEN, in neonatal rats subjected to hypoxic-ischemic brain damage (HIBD). By using Tat-K13 peptide to inhibit the PTEN nuclear translocation, the amelioration of motor and cognitive functions will be examined by using behavioral and electrophysiological approaches in HIBD rats. Furthermore, to reveal the cellular and molecular mechanisms of PTEN nuclear translocation induced by HIBD, we will also investigate the effects of HIBD on the mono-ubiquitination of PTEN, and the role of Nedd4-1 in PTEN nuclear translocation in primary cultured neurons. Knowledge gained from this study may provide new therapeutic targets and strategies for HIE.