Spinal stimulation modulates urethral sphincter activation in neurogenic bladders

 描述(申请人提供)：神经源性的外括约肌(EUS)收缩和松弛功能障碍是神经病理的结果，例如脊髓损伤(SCI)后逼尿肌括约肌协同失调(排尿时尿路阻力增加)，扰乱中枢神经系统对排尿反射的调节。这导致逼尿肌和EUS之间的不协调。各种神经调节方法被开发来调节下尿路(LUT)的功能，通过靶向位于腰骶水平的Onuf核。在这里，我们提出了一种新的方法，通过硬膜外刺激(EPS)在储尿期和排尿期之间调节EUS松弛来刺激脊髓EUS松弛控制中枢。脊柱EUS松弛控制中心将根据先前的发表(Chang等人，2007年)和初步结果，通过在多个上腰椎节段(L2-4)上使用EPS来确定。EPS对EUS松弛控制中枢的调节可能通过抑制EUS的紧张性收缩来促进排尿，即抑制尿路阻力。慢性脊髓损伤后，联合应用EPS和5-羟色胺能促进抑制EUS的紧张性收缩，进而引起排尿时的EUS松弛。EUS松弛控制中心的EPS为EUS激活在紧张性收缩和松弛之间切换提供了关键。LUT的功能评估将为慢性脊髓损伤后神经源性膀胱功能障碍的动物提供排尿效率的信息。通过EPS(生物工程方面)和/或5-羟色胺能调节(药理学方面)对EUS神经调节的拟议研究代表了一种利用神经源性膀胱改善LUT功能的前沿研究方法，也可用于降低伴有排尿功能受损的尿路阻力，如神经源性膀胱过度活动和活动不足的功能障碍、周围神经损伤和衰老。

 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.