神经炎症是导致继发性脊髓损伤的重要因素，小胶质细胞焦亡是介导脊髓损伤后神经炎症的重要部分，研究显示脊髓损伤后小胶质细胞发生焦亡，但机制不清。我们前期工作发现，脊髓损伤后，损伤处小胶质细胞焦亡，而且动物实验和细胞实验均证实脊髓损伤后circRNA-ITCH/microRNA-214/ caspase1轴的表达发生了明显的变化。由此推测，脊髓损伤后circRNA-ITCH/microRNA-214/caspase1轴通过介导小胶质细胞焦亡参与神经炎症，调控脊髓损伤的病理生理过程。本研究基于动物和细胞模型，采用荧光原位杂交、基因敲除、免疫组化等技术，证明circRNA-ITCH通过作为microRNA-214的竞争性海绵促进caspase1表达，介导小胶质细胞焦亡参与脊髓损伤的病理生理过程。本研究分析脊髓损伤后神经炎症的调节机制，可为临床上脊髓损伤的治疗提供实验依据。

Neuroinflammation is an important factor leading to secondary spinal cord injury, and pyroptosis of microglia is an important part of neuroinflammation after spinal cord injury. Previous studies reported that pyroptosis of microglia occurs after spinal cord injury. Howerver, the mechanism remains undefined. In our preliminary studies, we have obtained the exciting results showing that microglia cells in the injured area occured pyroptosis after spinal cord injury. Both animal and cell experiments confirmed that the expression of circRNA-ITCH/ microRNA-214/caspase1 axis changed significantly after spinal cord injury. We postulate that circRNA-ITCH/microRNA-214/caspase1 axis mediates pyroptosis of microglia cells, participates in neuroinflammation and regulates the pathophysiological process of spinal cord injury. In the current proposal, we will further explore the underlying mechanisms in both in vitro and in vivo models of spinal cord injury. The overall hypothesis is that circRNA-ITCH promotes the expression of caspase1 by acting as a competitive sponge for microRNA-214 and mediates pyroptosis of microglia cells in the pathophysiological process of spinal cord injury. A combination of state-of-the-art approaches including situ hybridization, gene knockout and immunohistochemistry method will be used to test this hypothesis. This project will analyze the regulatory mechanism of neuroinflammation after spinal cord injury, which can provide experimental basis for the treatment of clinical spinal cord injury.