Neurogenic bladder dysfunctions in neurological disorders

神经系统疾病中的神经源性膀胱功能障碍

• 批准号: 8720934
• 负责人: Anna P Malykhina
• 金额: $ 7.39万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-29 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8720934
• 关键词: Adrenergic Agents; Adrenergic Agonists; Affect; Afferent Neurons; Agonist; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Animal Model; Animals; Area; Basic Science; Behavioral; Bladder; Bladder Dysfunction; Brain; Brain Stem; Cells; Cellular biology; Central Nervous System Diseases; Clinic; Clinical; Clinical Sciences; Confocal Microscopy; Data; Demyelinations; Development; Diagnosis; Disease; Disease remission; Encephalomyelitis; Etiology; Evaluation; Filament; Flare; Frequencies; Functional disorder; Image Analysis; Immunohistochemistry; Impairment; In Vitro; Incontinence; Increased frequency of micturition; Interdisciplinary Study; Laboratories; Lesion; Location; Lower urinary tract; Microbiology; Modeling; Motor; Multiple Sclerosis; Murine hepatitis virus; Mus; Muscarinics; Nature; Nerve Degeneration; Nervous system structure; Neural Pathways; Neuraxis; Neurodegenerative Disorders; Neurogenic Bladder; Neurology; Neurons; Neurosciences; Neurotransmitter Receptor; Nocturia; Overactive Bladder; Parkinson Disease; Pathology; Pathway interactions; Patients; Peripheral; Pharmacology; Phenotype; Philadelphia; Pontine structure; Quality Control; Research; Research Infrastructure; Research Personnel; Research Project Grants; Sensory; Severities; Smooth Muscle; Spinal Cord; Spinal Ganglia; Stream; Symptoms; Techniques; Testing; Tissues; United States; Urination; Urine; Urology; Visceral; adrenergic; animal tissue; awake; base; disability; functional disability; functional status; in vivo; lower urinary tract symptoms; meetings; micturition urgency; midbrain central gray substance; mouse model; nervous system disorder; neurophysiology; neuroregulation; novel therapeutics; programs; receptor internalization; research study; response; therapeutic development; translational approach; treatment strategy; urologic; young adult

DESCRIPTION (provided by applicant): Patients with neurological disorders such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis develop a wide range of lower urinary tract symptoms (LUTS) including urinary urgency, frequency, incontinence, nocturia. Neurogenic bladder dysfunctions observed in patients with neurological disorders usually result from damage to the peripheral and/or central nervous systems. The lack of understanding of pathophysiology and mechanisms underlying LUT dysfunctions in neurological disorders hampers the development of therapeutic strategies and treatment options for these patients. In response to the RFA-DK-12-003, we propose to form the Philadelphia Interdisciplinary Research Center on Neurogenic Bladder Dysfunctions. The primary focus of the Center will be on understanding the systemic and cellular mechanisms of neurogenic bladder dysfunctions resulting from degeneration in the CNS in order to clarify functional interplay between the urologic and nervous systems. The Philadelphia Center will: a) provide the intellectual infrastructure to tackle on projects that will become comprehensive programs determining the underlying etiology of LUTS in neurological disorders; b) establish a well-integrated interdisciplinary research team of clinical and basic science researchers in the Greater Philadelphia area which will focus the research efforts on LUTS using animal models of neurogenic bladder dysfunctions; c) extend the phenotyping of LUTS from animal models to patients diagnosed with neurological disorders and complaining of LUTS, and d) generate preliminary data necessary to submit a program project (POI) after completion of this study. The research team will include established investigators with diverse expertise in neurourology, neurophysiology, pharmacology, microbiology, neurodegeneration, and clinical neurology. The Philadelphia IR-BU Center W\\\ consist of: 1) the laboratories of key investigators and their collaborators that combine expertise in neurology, neurourology, neurophysiology, cellular biology, microbiology, neuroscience, pharmacology, and pathology; 2) an Administrative Core to provide administrative and fiscal oversight, quality control for the research, coordination of interactions among key investigators in the Center and organization of monthly meetings; 3) an Animal tissue core to provide tissues from mice with different levels of neurodegeneration and demyelination for basic research projects; 4) an Educational Enrichment Program to attract young investigators to the field of urology and support their research in the laboratories of key investigators.

描述（由申请人提供）：患有神经系统疾病（例如多发性硬化症、帕金森病、阿尔茨海默病、肌萎缩侧索硬化症）的患者会出现多种下尿路症状（LUTS），包括尿急、尿频、尿失禁、夜尿。在患有神经系统疾病的患者中观察到的神经源性膀胱功能障碍通常是由于周围和/或中枢神经系统受损所致。对神经系统疾病中 LUT 功能障碍的病理生理学和机制缺乏了解，阻碍了针对这些患者的治疗策略和治疗方案的制定。为了响应 RFA-DK-12-003，我们提议成立费城神经源性膀胱功能障碍跨学科研究中心。该中心的主要重点是了解中枢神经系统退化引起的神经源性膀胱功能障碍的系统和细胞机制，以阐明泌尿系统和神经系统之间的功能相互作用。费城中心将： a) 提供知识基础设施来开展项目，这些项目将成为确定神经系统疾病中 LUTS 潜在病因的综合项目； b) 在大费城地区建立一个由临床和基础科学研究人员组成的综合性跨学科研究团队，重点研究使用神经源性膀胱功能障碍动物模型的 LUTS； c) 将 LUTS 表型分析从动物模型扩展到诊断为神经系统疾病并主诉 LUTS 的患者，以及 d) 生成完成本研究后提交计划项目 (POI) 所需的初步数据。该研究团队将包括在神经泌尿学、神经生理学、药理学、微生物学、神经退行性疾病和临床神经病学方面拥有不同专业知识的资深研究人员。费城 IR-BU 中心由以下组成： 1) 关键研究人员及其合作者的实验室，结合了神经学、神经泌尿学、神经生理学、细胞生物学、微生物学、神经科学、药理学和病理学方面的专业知识； 2) 行政核心，负责提供行政和财政监督、研究质量控制、中心主要研究人员之间的互动协调以及每月会议的组织； 3）动物组织核心，为基础研究项目提供不同程度神经变性和脱髓鞘小鼠的组织； 4) 教育丰富计划，吸引年轻研究人员进入泌尿外科领域并支持他们在关键研究人员实验室的研究。