权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Chemokines and Viral-Induced Neurologic Disease

趋化因子和病毒引起的神经系统疾病

基本信息

批准号：
8799945
负责人：
Thomas E Lane
金额：
$ 28.53万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-12-15 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8799945
关键词：
Acute Apoptosis Astrocytes Biology CD4 Positive T Lymphocytes CXC Chemokines CXCL1 gene CXCL10 gene CXCR3 gene CXCR4 Receptors Cell Death Cells Cessation of life Chemotactic Factors Chronic Chronic Disease Clinical Coronavirus Data Demyelinating Diseases Demyelinations Disease Encephalomyelitis Engraftment Etiology Funding Genetic Goals Health Histologic Host Defense Human Infection Infiltration Inflammatory Interleukin-8B Receptor Ligands Limb structure Link Lymphocyte Mediating Modeling Mononuclear Multiple Sclerosis Murine hepatitis virus Mus Myelin Nervous System Trauma Neuraxis Neuroglia Neurologic Oligodendroglia Operative Surgical Procedures Paralysed Pathogenesis Patients Physiological Population Receptor Signaling Research Proposals Role Severities Severity of illness Signal Transduction Stem cells Study models Symptoms System T-Lymphocyte Therapeutic Viral Viral hepatitis Virus Virus Diseases Work brain cell chemokine chemokine receptor macrophage migration nerve stem cell neuroinflammation neurotropic neurotropic virus novel novel therapeutic intervention oligodendrocyte lineage overexpression receptor remyelination repaired research study response sensitizing antigen virus-induced demyelination virus-induced neurologic disease white matter

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of this competitive renewal is to evaluate the functional role of chemokine and chemokine receptors in contributing to neurologic disease and repair following infection with a neurotropic murine coronavirus, mouse hepatitis virus (MHV). Infection of susceptible mice with MHV reproducibly results in an acute encephalomyelitis followed by a chronic demyelinating disease characterized clinically by ascending hind-limb paralysis and histologically by mononuclear cell infiltration into the central nervous system (CNS) accompanied by white matter destruction. Due to the similarities in clinical and histologic disease between MHV-induced demyelination and the human demyelinating disease multiple sclerosis (MS), the MHV system is considered an excellent model in which to study the underlying pathological mechanisms contributing to human demyelinating diseases such as MS. Similar to MS, both T cells and macrophages are thought to be important in contributing to white matter destruction. In addition, chemokine and chemokine receptors are expressed within the CNS of MS patients as well as MHV- infected mice indicating a prominent role in the pathogenesis of disease. Indeed, during the previous funding periods (initiated in 2000), we have defined functional roles for chemokines and chemokine receptors in regulating neuroinflammation that is involved in both host defense and demyelination in response to MHV infection by regulating lymphocyte and macrophage infiltration. The present proposal builds upon our previous work and offers the opportunity to define the functional role of chemokines and chemokine receptors in i) protecting oligodendrocytes (the myelin-producing cell of the CNS) from damage/death and ii) regulating the biology of engrafted neural progenitor cells e.g. positional migration and proliferation which contributes to axonal remyelination. Together, these studies will extend our current understanding of how chemokines and their receptors participate in protection and repair. Further, the data obtained from these experiments will identify potentially novel therapeutic approaches for treatment of MS as well as other human demyelinating diseases.

描述（由申请人提供）：本竞争性更新的长期目标是评估趋化因子和趋化因子受体在嗜神经性小鼠冠状病毒小鼠肝炎病毒（MHV）感染后促进神经系统疾病和修复中的功能作用。易感小鼠感染MHV可重复性地导致急性脑脊髓炎，随后出现慢性脱髓鞘疾病，临床表现为上行后肢瘫痪，组织学表现为单个核细胞浸润到中枢神经系统（CNS）并伴有白质破坏。由于MHV诱导的脱髓鞘与人类脱髓鞘疾病多发性硬化症（MS）在临床和组织学疾病上的相似性，MHV系统被认为是研究导致MS等人类脱髓鞘疾病的潜在病理机制的绝佳模型。与MS类似，T细胞和巨噬细胞被认为在白质破坏中起重要作用。此外，趋化因子和趋化因子受体在MS患者和MHV感染小鼠的中枢神经系统中表达，表明在疾病发病机制中起着突出作用。事实上，在之前的资助期间（始于2000年），我们已经确定了趋化因子和趋化因子受体在调节神经炎症中的功能作用，这些神经炎症涉及宿主防御和脱髓鞘，通过调节淋巴细胞和巨噬细胞浸润来响应MHV感染。目前的建议建立在我们之前的工作基础上，并提供了定义趋化因子和趋化因子受体在以下方面的功能作用的机会：1)保护少突胶质细胞（中枢神经系统的髓磷脂产生细胞）免受损伤/死亡；2)调节移植神经祖细胞的生物学，例如有助于轴突再髓鞘形成的位置迁移和增殖。总之，这些研究将扩展我们目前对趋化因子及其受体如何参与保护和修复的理解。此外，从这些实验中获得的数据将确定治疗多发性硬化症以及其他人类脱髓鞘疾病的潜在新治疗方法。