Regulation of Neuroinflammation after Peripheral Nerve Injury

周围神经损伤后神经炎症的调节

• 批准号: 10729778
• 负责人: Ashley L Kalinski
• 金额: $ 44.7万
• 依托单位: BALL STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-17 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10729778
• 关键词: Acute; Address; American; Anti-Inflammatory Agents; Axon; Axotomy; Biological Assay; Biology; Brain; Cell Communication; Cell Culture Techniques; Cell Reprogramming; Cells; Cellular biology; Central Nervous System; Chronic; Communication; Competence; Crush Injury; Data; Data Collection; Dendrites; Disease; Distal; Education; Educational process of instructing; Environment; Enzyme-Linked Immunosorbent Assay; Experimental Designs; Failure; Fibrinogen; Flow Cytometry; Goals; Immune; Immune response; Immune system; Immunology; Impairment; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Information Dissemination; Infrastructure; Injections; Injury; Intrinsic factor; Knowledge; Laboratories; Lead; Macrophage; Mediating; Medical; Mentors; Methods; Modeling; Molecular; Molecular Biology Techniques; Mus; Myeloid Cells; Natural regeneration; Nerve; Nervous System; Neuroglia; Neurons; Neurosciences; Pathway interactions; Peripheral Nervous System; Peripheral nerve injury; Play; Positioning Attribute; Postdoctoral Fellow; Recovery of Function; Regulation; Reporting; Research; Research Personnel; Rodent Model; Role; Schwann Cells; Signal Transduction; Site; Spinal Cord; Spinal Ganglia; Students; Supervision; System; Techniques; Testing; Therapeutic; Time; Tissues; Training; Transgenic Mice; Traumatic Nerve Injury; Traumatic injury; Universities; Wallerian Degeneration; Wild Type Mouse; Work; axon injury; axon regeneration; career; central nervous system injury; design; experience; experimental study; improved; inflammatory milieu; injured; innovative technologies; mouse model; nerve injury; neural repair; neuroimmunology; neuroinflammation; neuronal cell body; novel therapeutics; prevent; recruit; repaired; sciatic nerve; sciatic nerve injury; single-cell RNA sequencing; undergraduate student; wound healing

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.

项目概要 拟议的研究结合了分子神经科学和免疫学技术 研究损伤后神经系统和免疫系统之间的关系。 分为中枢神经系统（CNS），包括大脑和脊髓， 周围神经系统（PNS）是神经系统的主要细胞，由 3 个细胞组成。 组成部分：细胞体、用于短距离通信的树突以及使用的单个轴突 对于长距离通信，PNS 具有在轴突损伤后再生的能力，但这会失败。 发生在中枢神经系统损伤后，其结果通常是损伤后的长期功能缺陷。 神经免疫学领域的工作强调了炎症的二分性。 中枢神经系统和三七总皂甙损伤后激活和/或维持的通路这项工作表明。 炎症促进PNS再生，同时它是PNS再生的抑制因素之一。 中枢神经系统。 这项研究的长期目标是了解之间的关系 使用坐骨神经损伤的啮齿动物模型，免疫系统内的炎症和轴突再生。 重要的是，转基因小鼠模型的使用将表征空间和时间上的反应。 阐明组织驻留免疫细胞和血源性骨髓细胞在此期间的作用 此外，坐骨神经损伤模型以再生而闻名。 能力，这种能力将通过使用在 Wallerian 中显示失败的 Sarm1-/- 小鼠系来改变 沃勒变性是损伤后发生的一个重要的级联反应，在损伤中非常有效地发生。 PNS（但不在中枢神经系统中），并有助于清除碎片，以便轴突可以再生。这项工作将询问是否。 沃勒变性是炎症级联反应的触发因素，如果这对于轴突的发生至关重要 再生。 研究生将利用尖端的分子生物学技术来提出这些问题。 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 学生将获得可以提高制定中枢神经系统损伤治疗策略的能力的知识。 由Kalinski博士直接监督，将参与实验设计、数据收集、解释、 此外，所提议的部分实验将纳入到研究中。 Kalinski 博士教授的课程的实验室部分每年将覆盖另外 32 名学生。 卡林斯基实验室和她的班级的本科生和硕士生将被定位为 这些发现对理解免疫介导的神经修复有直接影响。 经验对他们毕业后追求职业和继续教育很有帮助。