Afferent Stimulation-Based Neural Prosthesis to Restore Bladder Function

描述 脊髓损伤(SCI)通常导致膀胱失去控制，导致无法有效地将尿留在膀胱内(尿失禁)，以及无法在排尿时完全排空膀胱。不完全的膀胱管理可能会导致感染，甚至肾功能衰竭，此外还有社交尴尬的情况。可用的治疗方法包括不良侧面 效果，为脊髓损伤人群留下了对使用有效神经假体设备的替代疗法的未得到满足的需求。该项目的目标有两个：1)探索感觉传入刺激作为恢复脊髓损伤后膀胱功能的一种手段，包括控制和排尿；2)培养Dennis Bourbeau成为领先的独立研究人员，恢复因脊髓损伤或其他神经疾病而丧失的功能。我们建议进行一项人类转化性研究，以研究慢性生殖器神经刺激以实现尿控，以及一项临床前慢性动物研究，以检查尿路内刺激以实现排尿。在人类翻译研究中，生殖神经的临床疗效 将对患有脊髓损伤的退伍军人进行刺激(GNS)评估。假设GNS将抑制膀胱反射亢进，这将表现为每日尿失禁次数和/或量的减少，所需导尿频率的减少，每日尿量的增加，以及尿动力学测量的膀胱容量的增加。表面电极将为神经节提供神经接口，其幅度是阈值的两倍，以唤起-肛门反射。在尿流动力学测试中，将直接和间接测量膀胱压力和容量，以响应GNS。这些指标将使用尿路内导管记录压力并允许液体流动，使用直肠内气囊导管测量腹压，使用表面肌电电极测量盆底活动。刺激参数建立后，受试者将被送回家，使用便携式GNS系统；他们将记录导尿和膀胱排尿事件的日记。这一目的将通过衡量其对脊髓损伤患者的功能益处来展示GNS系统的临床实用性。这些好处将与减少膀胱痉挛有关，从而减少大小便失禁。在临床前的慢性动物研究中，将对膀胱神经假体进行评估。这种神经假体将通过靶向慢性棘化猫远端尿路的感觉神经传入纤维来诱导膀胱排尿。该假说认为，尿路内感觉传入刺激会产生膀胱排空。我们将确定实现膀胱排尿的有效刺激参数，然后测量对尿道内感觉神经刺激的排尿量。比较感觉刺激后的起始量和排尿量将评估神经假体产生排尿的性能。这项研究是专门针对脊髓损伤人群的，并将把膀胱排尿的急性模型推进到慢性准备。这项工作将为基于感觉传入刺激的神经假体装置的开发提供新的见解，以恢复脊髓损伤后的膀胱功能。这项研究与Dennis Bourbeau的职业发展计划相结合，目标是培训成为一名领先的研究人员，重点是通过感觉刺激对盆腔自主功能丧失进行康复治疗。 公共卫生相关性： 该项目的主要目标是恢复患有脊髓损伤(SCI)或其他神经疾病的个人的膀胱功能。40%的SCI患者认为恢复他们的 将膀胱控制作为第一或第二优先事项(Anderson 2004)。对于那些完全失去膀胱控制的人，标准的护理治疗可能不能完全限制感染风险，每年的医疗费用超过20,000美元(法语，Campbell等人)。2007)。这一年度成本给每个人的个人财务和整个卫生保健系统带来了巨大的负担。超过15%的美国脊髓损伤患者是退伍军人(VA，2009年)，因此，维持他们的膀胱护理对退伍军人医疗保健来说是一个巨大的负担。提供改善的膀胱控制，这是这里提出的研究的最终目标，将提高患有脊髓损伤的退伍军人的生活质量，并减少对退伍军人医疗保健系统的经济影响。

DESCRIPTION Spinal cord injury (SCI) often leads to loss of bladder control, resulting in an inability to effectively keep urine in the bladder (incontinence) and an inability to completely empty the bladder when voiding. Incomplete bladder management can lead to infections and even renal failure, in addition to socially awkward situations. Available treatments include undesirable side effects, leaving an unmet need for an alternative therapy utilizing an effective neuroprosthetic device for the SCI population. The objective of this project is twofold: 1) To explore sensory afferent stimulation as a means of restoring bladder function, both continence and micturition, following SCI and 2) To train Dennis Bourbeau to become an leading independent research, restoring function lost to spinal cord injury or other neurological disorders. We propose a translational human study to examine chronic genital nerve stimulation to achieve urinary continence and a preclinical chronic animal study to examine intra-urethral stimulation to achieve micturition. In the human translational study, the clinical effectiveness of genital nerve stimulation (GNS) will be evaluated in veterans with SCI. The hypothesis is that GNS will inhibit bladder hyper-reflexia, which will be manifested in reduced frequency and/or volume of daily urinary incontinence, a decrease in the required frequency of catheterization, an increase in daily urine output and an increased bladder capacity as measured by urodynamics. Surface electrodes will provide the neural interface for GNS, with amplitudes at twice the threshold to evoke the pudendo-anal reflex. During urodynamics testing, bladder pressure and volume expressed will be measured directly and indirectly in response to GNS. These metrics will be observed using an intraurethral catheter to record pressure and to allow for fluid flow, an intrarectal balloon catheter to measure abdominal pressure, and surface electromyogram electrodes to measure pelvic floor activity. With stimulation parameters established, subjects will be sent home with a portable GNS system; they will keep a diary of catheterization and bladder voiding events. This aim will demonstrate the clinical utility of a GNS system by measuring its functional benefits for persons with SCI. These benefits will be related to decreased bladder spasticity, resulting in decreased episodes of incontinence. In the preclinical chronic animal study, a bladder neuroprosthesis will be evaluated. This neuroprosthesis will elicit bladder voiding by targeting sensory afferent fibers arising from the distal urethra in chronically spinalized cats. The hypothesis is that intra-urethral sensory afferent stimulation will produce bladder emptying. We will determine effective stimulation parameters for achieving bladder voiding, then measure voiding volumes in response to intra-urethral sensory nerve stimulation. A comparison between starting volumes and voiding volumes following sensory stimulation will evaluate the performance of the neuroprosthesis to produce micturition. This research is specifically targeted towards the SCI population and will advance an acute model for bladder voiding to a chronic preparation. This work will provide new insights for the development of a sensory afferent stimulation-based neuroprosthetic device to restore bladder function following spinal cord injury. This research is integrated with Dennis Bourbeau's career development plan with the goal of training to become a leading investigator, focusing on rehabilitative therapies for loss of pelvic autonomic functions through sensory stimulation. PUBLIC HEALTH RELEVANCE: The primary goal of this project is to restore bladder function for individuals with spinal cord injury (SCI) or other neurological disorders. Forty percent of people with SCI see restoring their bladder control as the first or second priority (Anderson 2004). For those who have lost full bladder control, standard treatments of care may not completely limit infection risks and have yearly healthcare costs over $20,000 (French, Campbell et al. 2007). This annual cost places a significant burden on each individual's personal finances and the health care system in general. Over 15% of the total U.S. population with SCI are veterans (VA 2009), thus maintaining their bladder care represents a significant load on veteran health care. Providing improved bladder control, as is the ultimate goal of the research proposed here, would enhance the quality of life for veterans with SCI and reduce the financial impact on the Veteran Health Care system.