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DEFECTS OF MUSCULAR INNERVATION IN NEUROGENIC BLADDER

神经源性膀胱肌肉神经支配缺陷

基本信息

批准号：
3117107
负责人：
AHMAD ELBADAWI
金额：
$ 8.45万
依托单位：
UPSTATE MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-30 至 1991-08-31
项目状态：
已结题

项目摘要

Neurogenic bladder dysfunction (NBD) is a significant public health problem, and a challenging area of urologic diagnosis and management. Two issues central to the problem are: (1) the lack of detailed information on the nature of intrinsic defects of muscular innervation in the dysfunctional bladder and urethra; (2) the very limited knowledge of mechanisms of neurotransmission in the vesicourethral musculature. This study addresses both of the above issues by a multimodal morphologic approach that has not been applied previously for this purpose. Short- and long-term changes in the neurohistochemistry and ultrastructure of muscular innervation in the detrusor, internal sphincter and rhabdosphincter (external urethral sphincter), in 6 experimental models of parasympathetic lower motoneuron-type NBD, will be analyzed both qualitatively and quantitatively, as a prelude to future morphologic study of human NBD. Correlation of the findings with a parallel analysis of innervation parameters in normal musculature using the same multimodal approach will provide new information relative to the first issue, namely, the nature of intrinsic defects of muscular innervation in the dysfunctional bladder and urethra. A subsequent correlative analysis of all morphologic data with available physiopharmacologic observations on normal and abnormal micturition will provide further new information relative to the second issue, namely, the structural basis of neurotransmission in the vesicourethral musculature. The results of the proposed study will thus fill important gaps in our knowledge of the neuromuscular basis of normal and abnormal micturition, and provide the hitherto lacking data base for the long-term objective, namely, the clinical morphologic study of muscular innervation in NBD in man, including that due to spinal cord injury. Such a study would eventually lead to the introduction of: (1) a clinical biopsy tissue test as an aid to diagnosis, treatment planning and follow-up; and (2) drug therapy options that are more selective, effective and predictable than has so far been available.

神经源性膀胱功能障碍（NBD）是一个重大的公共卫生问题，泌尿外科诊断和管理的一个具有挑战性的领域。两个核心问题问题是：（1）缺乏关于其性质的详细信息。功能失调的膀胱中肌肉神经支配的内在缺陷和尿道； (2) 对神经传递机制的了解非常有限膀胱尿道肌肉组织。本研究通过多模态形态学解决了上述两个问题以前没有为此目的应用过的方法。短和神经组织化学和肌肉超微结构的长期变化逼尿肌、内括约肌和横纹括约肌（外括约肌）的神经支配尿道括约肌），在 6 个副交感神经下段实验模型中运动神经元型 NBD，将进行定性和定量分析，如未来人类 NBD 形态学研究的前奏。研究结果的相关性使用正常肌肉组织的神经支配参数的并行分析相同的多模式方法将提供与第一种方法相关的新信息问题，即肌肉神经支配的内在缺陷的本质膀胱和尿道功能障碍。随后对所有内容进行相关分析形态学数据与可用的正常和正常的生理药理学观察排尿异常将提供与第二次相关的进一步新信息问题，即膀胱尿道神经传递的结构基础肌肉组织。因此，拟议研究的结果将填补我们知识的重要空白正常和异常排尿的神经肌肉基础，并提供迄今为止缺乏长期目标的数据库，即临床人类 NBD 肌肉神经支配的形态学研究，包括由于脊髓损伤。这样的研究最终将导致引入： (1) 临床活检组织测试，以辅助诊断、制定治疗计划和后续行动； (2) 更具选择性、更有效和更有效的药物治疗选择比迄今为止可用的更可预测。