PATHOGENESIS OF LYME NEUROBORRELIOSIS: STUDIES EX VIVO & IN VIVO

莱姆病神经疏螺旋体病的发病机制：离体研究

• 批准号: 8358068
• 负责人: MARIO TOMAS PHILIPP
• 金额: $ 3.72万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358068
• 关键词: Acute; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Apoptosis; Borrelia burgdorferi; CCL2 gene; CXCL13 gene; Cells; Cellular Infiltration; Cerebrospinal Fluid; Cranial nerve diseases; Dexamethasone; Encephalomyelitis; Enzyme-Linked Immunosorbent Assay; Exposure to; Funding; Ganglia; Grant; Histopathology; IL8 gene; Inflammation; Inflammation Mediators; Inflammatory; Interleukin-6; Lesion; Life; Lyme Disease; Lyme Neuroborreliosis; Lymphocyte; Macaca mulatta; Meningitis; National Center for Research Resources; Nerve; Neural Conduction; Neuraxis; Neuroglia; Neurons; Pathogenesis; Peripheral Nerves; Peripheral Nervous System; Pharmaceutical Preparations; Pleocytosis; Primates; Principal Investigator; Property; Radiculitis; Research; Research Infrastructure; Resources; Source; Tissues; United States National Institutes of Health; afferent nerve; cisterna magna; cost; in vivo; neuron apoptosis; satellite cell; spinal nerve posterior root

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early Lyme neuroborreliosis. This inflammatory context could potentiate glial and neuronal apoptosis both in the central and peripheral nervous systems (PNS). We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS), and dorsal root nerves and ganglia (DRG, PNS). ELISA of the cerebrospinal fluid (CSF) showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions. Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis. On the grounds of these results we inoculated 5 additional animals in the same fashion, and are performing peripheral nerve conduction studies. If DRG neurons are dying by apoptosis in vivo we expect to see changes in sensory nerve conduction properties. Moreover, if inflammation is involved in causing apoptosis, treatment of some of the animals with the anti-inflammatory drug dexamethasone may curb the alterations in nerve conduction properties.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 莱姆神经红细胞增多（LNB）可能表现为脑膜炎，颅神经病，急性辐射肌病变，或者很少作为脑脊髓炎。我们假设神经胶质在暴露于莱姆病剂Borrelia burgdorferi时会产生炎症介质，从而促进早期莱姆神经性雷神病的急性细胞浸润。这种炎症环境可以增强中枢神经系统和周围神经系统（PNS）的神经胶质和神经元凋亡。我们接种了活芽孢杆菌的活菌芽孢杆菌进入了恒河猕猴的甲壳虫，并检查了中枢神经系统（CNS）诱导的炎症变化，背根神经和神经节（DRG，PNS）。脑脊液（CSF）的ELISA早在接种后一周就显示出IL-6，IL-8，CCL2和CCL2和CXCL13的升高，主要伴有淋巴细胞和单核细胞性细胞增多症。 CSF细胞颗粒和中枢神经系统组织对B. burgdorferi培养阳性。组织病理学揭示了急性LNB的迹象：严重的多灶性瘦脑膜炎，辐射炎和DRG炎性病变。重要的是，感染动物的DRG显示出明显的卫星细胞和神经元细胞凋亡。基于这些结果，我们以相同的方式接种了5种其他动物，并正在进行周围神经传导研究。如果DRG神经元因体内凋亡而死，我们希望看到感觉神经传导性能的变化。此外，如果引起凋亡涉及炎症，则用抗炎药物地塞米松治疗一些动物可能会遏制神经传导性能的改变。