Zebrafish Models of CNS Injury and Locomotor Recovery

人脊髓损伤（SCI）影响多种细胞类型，在初始损伤后，细胞和生化机制的自我传播级联导致额外的组织损失，从而加剧了SCI。斑马鱼中枢神经系统（CNS）与哺乳动物共享许多组织、细胞和分子途径；然而，斑马鱼即使在脊髓完全切断后，功能再生也会发生。我们对斑马鱼的中枢神经系统如何对损伤作出反应并随后再生的理解仍然不完整。我们的长期目标是利用光遗传学工具和斑马鱼模型来推进我们对神经损伤的细胞反应和随后的再生过程的理解。本研究计划的科学目的是：(1)确定不同类型损伤后发生的细胞事件；(2)确定作为运动恢复基础的生物电网络的变化。本项目将建立一个框架，利用斑马鱼幼体作为神经损伤和神经变性研究的模型。研究完成后，有望对运动恢复的生物学基础提供更全面的了解，并提供新的治疗干预点。

Human spinal cord injuries (SCIs) affect multiple cell types and after the initial injury, a self-propagating cascade of cellular and biochemical mechanisms lead to additional tissue loss that exacerbates the SCI. The zebrafish central nervous system (CNS) shares many organizational, cellular and molecular pathways with mammals; however, functional regeneration occurs in zebrafish even after complete transection of the spinal cord. Our understanding of how the CNS of zebrafish responds to injury and subsequently regenerates remains incomplete. Our long-term goal is to advance our understanding of the cellular response to neural injury and subsequent process of regeneration using optogenetic tools and zebrafish models. The scientific aims of this research plan are to: (1) identify the cellular events that occur after different types of injury and (2) determine changes in the bioelectric network as the basis for locomotor recovery. This project will establish a framework to utilize the zebrafish larvae as a model for studies in neural injury and neurodegeneration. Upon completion, the proposed research is expected to provide a more complete picture of the biological basis for locomotor recovery and provide new therapeutic intervention points.