新生儿缺氧缺血是新生儿死亡和儿童神经伤残的重要原因之一，促进受损神经细胞的修复是目前研究热点。研究发现双皮质素（DCX）通过调控轴突运输可促进受损视神经的存活和再生。但DCX在其他中枢神经中的作用和机制仍不明确。大量研究表明缺氧缺血后DCX在受损大脑不同部位包括海马中明显增加。我们推测DCX的增加可促进缺氧缺血后受损海马神经细胞的存活和再生。本课题拟利用新生小鼠缺氧缺血模型，通过体外神经培养和实时显微记录，来验证我们的假设并揭示其作用机理：1.DCX促进哪些受损海马神经细胞的存活和再生，神经前体细胞还是分化成熟细胞？2.DCX是否通过驱动蛋白KIF1A和动力蛋白dynein调控轴突运输来影响细胞存活和再生？影响到哪些下游靶点？3.已知的DCX不同位点的磷酸化修饰是否参与受损神经修复？本课题的研究有望为治疗新生儿缺氧缺血性脑病提供新的思路，也为其它神经损伤后的再生难题提供新的方向和理论基础。

Neonatal hypoxia-ischemia is one of the important causes of neonatal death and neurological disability in children。Promoting the survival and regeneration of damaged neuron is one of the therapeutic approaches. Research indicates that doublecortin (DCX) promotes survival and regeneration of damaged optic neuron through regulating axonal transport. However, the role and mechanism of DCX in other central neurons remains unclear. Many studies demonstrate that DCX is increased in different areas of neonatal brain after hypoxic-ischemia. We hypothesize that an increase in DCX after hypoxia-ischemia can promote the survival and regeneration of hippocampal neurons. We intend to use neonatal hypoxia-ischemia mouse model, in vitro neuronal culture and live imaging to verify our hypothesis and reveal the molecular mechanism: 1. Which type of cell can DCX promote its survival and regeneration, neural precursor cell or mature neuron? 2. How does DCX affect cell survival and regeneration through KIF1A and dynein regulated axonal transport? What are the downstream targets? 3. Is phosphorylation status of DCX protein involved in the regulation of neuronal survival and regeneration? We hope this study will provide not only new insights for the clinical treatment of neonatal hypoxic ischemic encephalopathy, but also a new direction and theoretical basis for other regeneration problems after central nervous system injury.