脊髓损伤后神经炎症反应在继发性损伤中起重要作用，会妨碍神经的修复再生，最终形成脊髓软化、坏死囊腔或胶质瘢痕。我们前期研究表明，CDNF可通过抑制JNK活化及PGE2的表达来调控脊髓损伤后神经炎症反应，促进轴突再生。在此基础上，本项目旨在阐明CDNF对神经炎症的调控及其机制，探索CDNF的膜表面受体及其分子机制：可能是通过激活RTK, 从而活化PI3K，抑制MAPKK-JNK-c-Jun从而减少PGE2等炎症介质的释放；并研究CDNF对脊髓损伤后小胶质细胞活化的调控，探讨其对小胶质细胞介导的神经炎症的影响和机制。最终揭示CDNF在脊髓损伤神经炎症中的保护作用机制：是通过RTK-PI3K-JNK信号调控COX-2-PGE2通路，抑制小胶质细胞的过度活化、过度炎症反应及胶质瘢痕形成，改善损伤局部微环境，促进神经轴突再生和脊髓功能恢复。为其用于治疗脊髓损伤和促进神经再生提供理论依据和新的治疗策略。

The neuroinflammation after spinal cord injury (SCI) causes myelomalacia, necrotic cavity and glial scarring, which hampering the nerve regeneration. Our previous data showed that CDNF regulated neuroinflammation and promoted axonal regeneration by suppressing JNK activation and PGE2 production. Based on that, this project aims to illuminate the mechanism of CDNF regulating neuroinflammation. The membrane receptor of CDNF may be RTK, which can activate PI3K, and then suppress MAPKK-JNK-c-Jun and the expression of PGE2. We also explore mechanism of CDNF regulating the activation of microglia in spinal cord injury. Ultimately, we illustrate that CDNF shows protective role in neuroinflammation of spinal cord injury by RTK-PI3K-JNK regulating COX-2-PGE2 signaling, which suppressing the activation of microglia, neuroinflammation, and glial scarring, improving the microenvironment and promoting the axonal regeneration and functional recovery. This will present a novel promising strategy for the treatment of spinal cord injury.