Suprapontine Control of Micturition

桥上排尿控制

• 批准号: 6685983
• 负责人: JAMES R ROPPOLO
• 金额: $ 27.94万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-15 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6685983
• 关键词: Suprapontine; Control; Micturition

DESCRIPTION (provided by applicant): The storage and periodic release of urine is controlled from several levels of the central nervous system (CNS) including the lumbosacral spinal cord, rostral pons, hypothalamus, subcotical nuclei, and the cerebral cortex. Various evidence indicates that the excitatory parasympathetic component of the mictudtion reflex is dependent upon supraspinal pathway originating in the rostral pons ("pontine micturition center" - PMC) and sending descending fibers to the sacral spinal cord. The studies outlined in the present proposal are designed to provide a detail analysis, using modem neuroanatomical, neurophar macological and neurophysisological techniques, of pontine and suprapontine structures which modulate the micturition reflex pathway. The aims of this proposed research are: 1) To determine, using electrical stimulation, sites within the cortex, hypothalamus, and areas adjacent to hypothalamus which modulate bladder reflexes. 2) To examine the effects of L-glutamate microinjected into those sites which give positive results (either inhibition or facilitation) with electrical stimulation. (L-glutamate witl be used here as pharmacological tool to determine whether cell bodies or axons-in-passage are being activated by the electrical stimulation - L-glutamate being active only at cell bodies.) 3) To study in detail the modulation by hypothalamic and cortical sites on: a) isometric rhythmic bladder contractions, b) voiding cystometrogram (CMG), c) sympathetic input to bladder via the hypogastric nerve, d) electromyogram (EMG) of the external urethral sphincter, e) reflex evoked activity to pelvic nerve stimulation and f) single and multiunit activity at the level of the PMC and pelvic nerve efferents. 4) To determine using immunohistochemical techniques the possible neurotransmitters which mediate modulation by these suprapontine sites, and to follow these studies with neuropharmacological studies to determine the effects of agonist and especially antagonist of these putative neurotransmitters mediating the modulatory effects. 5) To determine the location of neurons in pontine and suprapontine structures (especially cortical and hypothalamic sites) which express the oncogene C-los to electrical stimulation of bladder afferents. The information gained in this study will not only provide a much more complete wiring diagram for the micturition pathway but may also suggest possible pharmacological modification of the act of micturition.

描述（由申请人提供）：尿液的储存和定期释放由中枢神经系统（CNS）的几个水平控制，包括腰骶脊髓、脑桥吻侧、下丘脑、皮质下核和大脑皮层。 各种证据表明，排尿反射的兴奋性副交感神经成分依赖于起源于脑桥头侧（“脑桥排尿中心”- PMC）并将下行纤维发送到骶脊髓的脊髓上通路。 本建议中概述的研究旨在使用现代神经解剖学、神经药理学和神经生理学技术，对调节排尿反射通路的脑桥和脑桥上结构进行详细分析。 本研究的目的是：1）确定，使用电刺激，在皮质，下丘脑，下丘脑附近的区域，调节膀胱反射的网站。2)研究在电刺激产生阳性结果（抑制或易化）的部位微量注射L-谷氨酸的作用。（L-谷氨酸在此用作药理学工具，以确定细胞体或通道中的轴突是否被电刺激激活-L-谷氨酸仅在细胞体处有活性。3)详细研究下丘脑和皮质部位对下列活动的调制：a）等长节律性膀胱收缩，B）排尿膀胱测压图（CMG），c）经腹下神经向膀胱的交感神经输入，d）尿道外括约肌肌电图（EMG），e）对盆神经刺激的反射诱发活动，f）PMC和盆神经传出水平的单个和多单位活动。4)使用免疫组织化学技术确定可能的神经递质介导的调制这些脑桥上的网站，并遵循这些研究与神经药理学研究，以确定这些假定的神经递质的激动剂，特别是拮抗剂介导的调节作用的影响。5)确定表达癌基因C-los的神经元在脑桥和脑桥上结构（特别是皮质和下丘脑部位）中对膀胱传入神经电刺激的位置。本研究中获得的信息不仅将提供更完整的排尿通路接线图，还可能提示可能的排尿行为药理学修饰。