Spinal stimulation modulates urethral sphincter activation in neurogenic bladders

脊髓刺激调节神经源性膀胱中尿道括约肌的激活

• 批准号: 8942449
• 负责人: Huiyi Harriet Chang
• 金额: $ 34.8万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8942449
• 关键词: Acute; Adult; Aging; Agonist; Anatomy; Animals; Ataxia; Bioinformatics; Biomedical Engineering; Bladder; Bladder Dysfunction; Cell Nucleus; Chronic; Clinical; Complex; Data Set; Electromyography; Evaluation; Feasibility Studies; Frequencies; Functional disorder; Infusion procedures; Investigation; Location; Lower urinary tract; Lumbar spinal cord structure; Maps; Metabolic; Methods; Micturition Reflex; Monitor; Motor Neurons; Nerve; Neuraxis; Neurogenic Bladder; Neurons; Pathway interactions; Pelvis; Peripheral nerve injury; Pharmacology; Phase; Physiology; Publications; Rattus; Reflex action; Regulation; Relaxation; Research; Research Personnel; Research Project Grants; Resistance; Serotonin Agents; Sphincter; Spinal; Spinal Cord; Spinal Cord transection injury; Spinal cord injury; Syndrome; Thoracic spinal cord structure; Trauma; Urethra; Urethral sphincter; Urination; Urine; Urodynamics; base; improved; nervous system disorder; neurological pathology; neurophysiology; neuroregulation; novel; novel strategies; public health relevance; receptor; research study; response; urologic

 DESCRIPTION (provided by applicant): Neurogenic dysfunction of external urethral sphincter (EUS) contraction and relaxation is a consequence of neurological pathology such as detrusor sphincter dyssynergia (increase of urethral resistance during voiding) after spinal cord injury (SCI) that disrupts central nervous system regulation of micturition reflexes. This results in dys-coordination between detrusor and EUS. A variety of neuromodulation approaches are developed to modulate the lower urinary tract (LUT) function by targeting the Onuf's nucleus located at lumbosacral levels. Here, we propose a novel method on stimulating spinal EUS relaxation controlling center by using epidural stimulation (EpS) to modulate EUS relaxation between storage and voiding phases. Spinal EUS relaxation controlling center will be identified by using EpS over several upper lumbar levels (L2-4) based on the previous publication (Chang et al., 2007) and preliminary results. Modulation of EUS relaxation controlling center by EpS possibly facilitates voiding by suppressing EUS tonic contraction, in other words, inhibits urethral resistance. After chronic SCI, a combination of EpS and serotonergic input promotes the suppression of EUS tonic contraction and further evokes the EUS relaxation during voiding. EpS of EUS relaxation controlling center provides the key for switching EUS activation between tonic contraction and relaxation. Functional assessment of LUT will be investigated to provide the information of voiding efficiency in the animals with neurogenic bladder dysfunction after chronic SCI. The proposed study focusing on EUS neuromodulation by using EpS (bioengineering aspect) and/or serotonergic modulation (pharmacological aspect) represents a cutting-edge research approach to improve LUT function with neurogenic bladder, and can be also used to reduce urethral resistance with impaired voiding contractions such as neurogenic bladder dysfunction of overactive and underactive bladders, peripheral nerve injuries, and aging.

 描述（由申请人提供）：尿道外括约肌（EUS）收缩和舒张的神经源性功能障碍是神经病理学的结果，例如脊髓损伤（SCI）后逼尿肌括约肌协同失调（排尿期间尿道阻力增加），破坏了中枢神经系统对排尿反射的调节。这导致逼尿肌和 EUS 之间的协调失调。人们开发了多种神经调节方法，通过针对位于腰骶部的 Onuf 核来调节下尿路 (LUT) 功能。在这里，我们提出了一种通过使用硬膜外刺激（EpS）来刺激脊柱 EUS 松弛控制中心的新方法，以调节存储阶段和排尿阶段之间的 EUS 松弛。根据之前的出版物（Chang 等，2007）和初步结果，将通过使用 EpS 在几个上腰椎水平（L2-4）上识别脊柱 EUS 松弛控制中心。 EpS对EUS松弛控制中心的调节可能通过抑制EUS强直收缩来促进排尿，换句话说，抑制尿道阻力。慢性 SCI 后，EpS 和血清素输入的结合促进了 EUS 强直收缩的抑制，并进一步引起排尿期间 EUS 松弛。 EUS放松控制中枢的EpS提供了EUS激活在强直收缩和放松之间切换的关键。将研究 LUT 的功能评估，以提供慢性 SCI 后神经源性膀胱功能障碍动物的排尿效率信息。拟议的研究重点是通过使用 EpS（生物工程方面）和/或血清素能调节（药理学方面）进行 EUS 神经调节，代表了一种改善神经源性膀胱 LUT 功能的前沿研究方法，也可用于减少排尿收缩受损的尿道阻力，例如膀胱过度活动和活动不足的神经源性膀胱功能障碍、周围神经 受伤、衰老。