Spinal stimulation modulates urethral sphincter activation in neurogenic bladders

 描述（由申请人提供）：神经源性尿道外括约肌（EUS）收缩和舒张功能障碍是神经病理学的结果，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。通过靶向位于腰骶水平的Onuf核，开发了多种神经调节方法来调节下尿路（LUT）功能。在此，我们提出了一种新的方法，通过硬膜外刺激（EpS）刺激脊髓EUS松弛控制中心来调节EUS在存储和排尿相之间的松弛。脊柱EUS松弛控制中心将基于先前的出版物（Chang等人，2007年，取得初步成果。EpS对EUS舒张控制中枢的调节可能通过抑制EUS的紧张性收缩而促进排尿，即抑制尿道阻力。在慢性SCI后，EpS和肾上腺素能输入的组合促进了EUS紧张性收缩的抑制，并进一步引起排尿时的EUS松弛。EUS舒张控制中枢的EpS是EUS在紧张性收缩和舒张之间转换激活的关键。本研究将探讨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的信息。通过使用EpS（生物工程方面）和/或EUS能调节（药理学方面）重点关注EUS神经调节的拟议研究代表了改善神经源性膀胱LUT功能的前沿研究方法，也可用于降低排尿收缩受损的尿道阻力，如过度活动和活动不足膀胱的神经源性膀胱功能障碍、外周神经损伤和衰老。

 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.