BLADDER OUTLET OBSTRUCTION INDUCED NEUROPLASTICITY

说明(申请人提供)良性前列腺增生症(BPH) 最常见的原因是膀胱流出道梗阻(BOO)。这个条件是 通常与不受抑制的膀胱收缩有关。刺激性的 排尿症状，不受抑制的膀胱收缩的后果是非常 令一大群老年男性感到困扰，对他们的 生活质量。这项研究提案的总体假设是 排尿功能的神经控制在以下方面发生显著变化 良性前列腺增生症是由多种因素介导的，包括：(1)属性的改变 外周器官(膀胱)对膀胱传入神经元的影响 功能障碍和(2)脑内神经元间质特性的变化 脊髓。因此，我们建议脊柱排尿的重组 神经回路是对神经-靶器官相互作用的变化作出反应。我们 计划检查BOO对神经化学、组织和 中枢神经系统中传入和脊髓神经元的形态特征 排尿反射通路。这项研究提案旨在提供更多的 透彻了解下尿路反射的配线图 以及神经递质在这些反射中的功能。 在我们研究的第一部分，我们将评估神经元的神经化学变化。 参与排尿反射，在BOO之后投射到外周。 将识别投射到膀胱的外周和脊髓神经元 在将示踪剂注入膀胱后。后来， 免疫组织化学技术将用于确定血管内皮细胞 神经活性物质在这些神经元中的表达。 第二组实验将使用药理学技术来评估 神经活性物质在中枢排尿通路中的作用 慢性嘘声。这些神经活性化合物的选择性抑制剂的作用 关于BOO后和假手术对照组的排尿反射将是 用膀胱测压技术测定(记录压力变化 充盈和排尿时的膀胱)。 在本研究项目的第三部分，我们建议确定 膀胱中间神经元和副交感神经节前神经元的组织 大脑中的神经元。腰骶部脊髓。网络之间的连接性变化 在BOO之后，将对各种脊柱要素进行评估。

DESCRIPTION (provided by applicant) Benign prostatic hyperplasia (BPH) is the most common cause of bladder outflow obstruction (BOO). This condition is commonly associated with uninhibited urinary bladder contractions. Irritative voiding symptoms, a consequence of uninhibited bladder contractions are very bothersome to a large population of aging men, adversely affecting their quality of life. The overall hypothesis for this research proposal is that the marked changes in the neural control of voiding function that occur following BPH are mediated by multiple factors, including: (1) changes in the properties of urinary bladder afferent neurons induced by peripheral organ (bladder) dysfunction and (2) changes in the properties of interneuronal populations in the spinal cord. Thus, we propose that reorganization of spinal micturition circuitry occurs in response to changes in neural-target organ interactions. We plan to examine the effects of BOO on the neurochemical, organizational and morphological properties of afferent and spinal neurons involved in the micturition reflex pathway. This research proposal aims to provide a more thorough understanding of the wiring diagram for lower urinary tract reflexes and the functions of neurotransmitters in these reflexes. In the first part of our study we will assess neurochemical changes in neurons involved in the micturition reflex that project to the periphery following BOO. Peripheral and spinal neurons projecting to the bladder will be identified following injection of the tracer into the urinary bladder. Subsequently, immunohistochemical techniques will be used to determine changes in the expression of neuroactive compounds in these neurons. A second group of experiments will use pharmacological techniques to evaluate the role of neuroactive compounds in the central micturition pathway following chronic BOO. The effect of selective inhibitors of these neuroactive compounds on the micturition reflexes following BOO and in sham-operated controls will be determined with the use of the cystometrography (recording pressure changes in the urinary bladder during filling and micturition). In the third part of this research project, we propose to determine the organization of urinary bladder interneurons and parasympathetic preganglionic neurons in the. lumbosacral spinal cord. Changes in connectivity between the various spinal elements will be assessed following BOO.