BLADDER OUTLET OBSTRUCTION INDUCED NEUROPLASTICITY

描述（由申请人提供）良性前列腺增生（BPH）是 膀胱流出道梗阻（BOO）的最常见原因。该条件 通常与不受抑制的膀胱收缩有关。刺激性 排尿症状，不受抑制的膀胱收缩的后果是非常 对大量老年人来说是一个麻烦，对他们的生活产生不利影响。 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发生显著变化， BPH是由多种因素介导的，包括：（1）性质的改变 外周器官（膀胱）诱发的膀胱传入神经元 功能障碍和（2）在中间神经元群体的性质的变化， 脊髓因此，我们认为脊髓排尿的重组 电路响应于神经-靶器官相互作用的变化而发生。我们 计划检查BOO对神经化学，组织和 参与的传入和脊髓神经元的形态学特性 排尿反射通路这项研究旨在提供一个更 彻底了解下尿路反射的接线图 以及神经递质在这些反射中的作用。 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BOO后投射到外周的排尿反射。 将识别投射到膀胱的外周和脊髓神经元 在将示踪剂注射到膀胱中之后。随后，委员会注意到， 免疫组织化学技术将被用来确定的变化， 这些神经元中神经活性化合物的表达。 第二组实验将使用药理学技术来评估 神经活性化合物在中枢排尿通路中的作用 慢性BOO。这些神经活性化合物的选择性抑制剂的作用 对BOO后排尿反射和假手术对照的影响 使用膀胱测压法（记录膀胱内的压力变化）测定 在充盈和排尿期间的膀胱）。 在本研究项目的第三部分中，我们建议确定 膀胱中间神经元和副交感节前神经元的组织 的神经元。腰骶脊髓之间的连通性变化 在BOO之后将评估各种脊柱元件。

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.