Regulation of Neuroinflammation after Peripheral Nerve Injury

项目摘要 这项拟议中的研究将分子神经科学和免疫学技术相结合， 探讨创伤后神经系统与免疫系统的关系。神经系统 分为中枢神经系统（CNS），包括大脑和脊髓，以及 外周神经系统（PNS）。神经元是神经系统的主要细胞，由3个 部分：细胞体，用于短距离通信的树突，以及用于短距离通信的单个轴突。 用于远距离通信。PNS具有轴突损伤后再生的能力，而这失败了。 发生在中枢神经系统损伤后。其结果通常是长期的功能缺陷后受伤， 大脑和脊髓神经免疫学领域的工作强调了炎症反应的二分法。 在CNS和PNS损伤后被激活和/或持续的通路。这项工作表明， 炎症促进PNS的再生，而炎症是PNS再生的抑制因素之一。 CNS。 这项研究的长期目标是了解 炎症和PNS内的轴突再生。使用啮齿动物坐骨神经损伤模型，免疫 将表征空间和时间上的响应。重要的是，使用转基因小鼠模型将 阐明了组织驻留免疫细胞和血源性骨髓细胞在这一过程中的作用， 炎症级联反应此外，虽然坐骨神经损伤模型是众所周知的再生 胜任，此胜任将通过使用显示Wallerian中失败的Sarm 1-/- mouse行进行更改 退化沃勒变性是损伤后的一个重要级联反应，其在神经系统中非常有效地发生。 PNS（但不在CNS中），并有助于清除碎片，使轴突可以再生。这项工作将问是否 沃勒变性是炎症级联反应的触发器，如果这对轴突至关重要， 再生 研究生将利用尖端的分子生物学技术来问这些问题。他们的 研究结果将有助于理解炎症介导的神经修复，并有助于填补一些空白， 这些知识可以提高开发CNS损伤治疗策略的能力。学生将 由Kalinski博士直接监督，并将参与实验设计，数据收集，解释， 和传播成果。此外，所提议的部分实验将纳入 卡林斯基博士教授的课程的实验室部分，每年将增加32名学生。 卡林斯基实验室和她班上的本科生和硕士生将被定位为 这些发现对免疫介导的神经修复的理解有直接影响。这些 这些经验对他们毕业后的职业发展和继续教育大有裨益。

Project Summary The proposed research uses a combination of molecular neuroscience and immunology techniques to investigate the relationship between the nervous system and immune system after injury. The nervous system is divided into the central nervous system (CNS), which includes the brain and the spinal cord, and the peripheral nervous system (PNS). Neurons are the main cells of the nervous system and are composed of 3 parts: a cell body, dendrites that are used for short-distance communication, and a single axon which is used for long distance communication. The PNS has the ability to regenerate following axonal injury, while this fails to occur in after injury to the CNS. The result of this is usually long-term functional deficits following injuries to the brain and spinal cord. Work within the neuroimmunology field has highlighted a dichotomy in inflammatory pathways that are activated and/or sustained following injury to the CNS and the PNS. This work suggests that inflammation promotes regeneration in the PNS, while it is one of the inhibitory factors to regeneration in the CNS. The long-term objective of this proposed research is to understand the relationship between inflammation and axon regeneration within the PNS. Using rodent models of sciatic nerve injury, the immune response both spatially and temporally will be characterized. Importantly, use of transgenic mouse models will elucidate the roles that both tissue resident immune cells and blood-borne myeloid cells have during this inflammatory cascade. Further, while the sciatic nerve injury model is well known for being regeneration competent, this competency will be altered by utilizing the Sarm1-/- mouse line that shows a failure in Wallerian degeneration. Wallerian degeneration is an important cascade following injury that occurs very efficiently in the PNS (but not in the CNS), and helps remove debris so the axons can regenerate. This work will ask whether Wallerian degeneration is the trigger for the inflammatory cascade and if this is essential for axons to regenerate. Research students will utilize cutting edge molecular biology techniques to ask these questions. Their findings will contribute to understanding of inflammatory mediated neural repair and help fill in several gaps in knowledge that could improve the ability to develop therapeutic strategies for CNS injuries. Students will be directly supervised by Dr. Kalinski and will participate in experimental design, data collection, interpretation, and dissemination of results. Furthermore, portions of the experiments proposed will be incorporated into the laboratory components of a course taught by Dr. Kalinski that will reach an additional 32 students a year. Undergraduate and master’s students in the Kalinski laboratory and in her class will be positioned to make discoveries that have a direct impact on the understanding of immune mediated neural repair. These experiences will serve them well as they pursue careers and further education after graduation.