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.

项目总结