Neural Prosthetic Control of Continence and Micturition

描述（由申请人提供）：由于神经系统疾病或损伤（如脊髓损伤（SCI））导致的膀胱控制丧失具有破坏性影响。脊髓损伤导致膀胱排空失去自主控制，膀胱反射过度和膀胱括约肌协同作用障碍。这些因素通常会导致输尿管反流和梗阻、肾脏感染、长期肾脏损害、自主神经反射障碍发作并伴有血压危险升高、导致皮肤破裂的尿失禁以及频繁的尿路感染。膀胱失控还会产生深远的社会影响，导致生活质量下降，以及从手术、用品和药物方面产生的大量直接医疗费用。本研究的长期目标是开发一种神经假体，以恢复神经系统疾病，特别是脊髓损伤患者的膀胱功能（失禁和排尿）。我们正在寻求一种创新的方法，利用电刺激阴部神经（及其分支）的传入（感觉）纤维，参与脊髓反射，抑制膀胱维持自制或激活膀胱产生排尿。这种新方法与先前使用脊髓根电刺激的方法有很大的不同，因为它不需要脊髓板切除术，不需要对骶感觉神经根进行不可逆转的手术切除，并且刺激系统的传入而不是传出侧。在第一个资助期间，我们开发和评估了一个闭环控制系统，以改善动物和脊髓损伤患者的失禁，我们发现并量化了反射的特性，在阴部传入刺激下激活膀胱，我们确定了手术进入阴部神经的途径，并且神经可以进行袖带植入。设计了一种平面界面神经电极，用于选择性刺激人类阴部神经。本建议的总体目标是通过电刺激阴部传入神经来提高膀胱排空的效率。在前一阶段，我们发现并描述了两种反射，当阴部传入神经受到电刺激时，它们会刺激膀胱，抑制括约肌，并产生排尿。然而，获得的排尿是有限的，并且在慢性脊髓损伤患者中，阴部传入神经的激活会产生小幅度或短暂的膀胱收缩。因此，我们将通过动物模型和脊髓损伤患者的补充实验，开发和评估几种新方法来增强阴部传入刺激引起的膀胱排空。该项目的成功完成将促进有效的膀胱功能修复神经修复系统的发展。

DESCRIPTION (provided by applicant): Loss of bladder control as a result of neurological disease or injury such as spinal cord injury (SCI) has devastating effects. SCI results in loss of voluntary control of bladder evacuation, bladder hyper-reflexia, and bladder sphincter dysynergia. These factors often lead to ureteric reflux and obstruction, infection of the kidneys, long-term renal damage, episodes of autonomic dysreflexia with dangerous rises in blood pressure, incontinence which contributes to skin breakdown, as well as frequent urinary tract infections. Loss of bladder control also has profound social impact and leads to decreased quality of life, as well as large direct medical costs from procedures, supplies, and medication. The long-term goal of this research is to develop a neural prosthesis to restore bladder function (continence and micturition) in persons with neurological disorders, particularly spinal cord injury. We are pursuing an innovative approach using electrical stimulation of afferent (sensory) fibers in the pudendal nerve (and its branches) that engage spinal reflexes that either inhibit the bladder to maintain continence or activate the bladder to produce micturition. This novel approach differs substantially from prior approaches using electrical stimulation of the spinal roots in that it does not require a spinal laminectomy, does not require irreversible surgical transection of the sacral sensory nerve roots, and stimulates the afferent rather than the efferent side of the system. During the first funding period we developed and evaluated a closed-loop control system to improve continence in both animals and in persons with spinal cord injury, we discovered and quantified the properties of reflexes that activated the bladder in response to pudendal afferent stimulation, we determined the surgical access to the pudendal n. and that the nerve is amenable to cuff implantation, and we designed a flat interface nerve electrode for selective stimulation of the human pudendal nerve. The overall objective of the present proposal is to increase the efficiency of bladder emptying achieved by electrical stimulation of pudendal afferents. In the previous period we discovered and characterized two reflexes that when activated by electrical stimulation of pudendal afferents excite the bladder, inhibit the sphincter, and produce micturition. However, the voiding that was achieved was limited, and in persons with chronic SCI, activation of pudendal afferents produced small amplitude or transient contractions of the bladder. Therefore, we will develop and evaluate several novel approaches to enhance bladder emptying induced by pudendal afferent stimulation through complementary experiments in an animal model and in persons with spinal cord injury. Successful completion of this project will advance the development of an effective neural prosthetic system for restoration of bladder function.