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)而导致的膀胱控制丧失，具有毁灭性的影响。脊髓损伤导致失去对膀胱排空的自主控制，膀胱反射亢进和膀胱括约肌协同障碍。这些因素通常导致输尿管返流和梗阻、肾脏感染、长期肾脏损伤、自主神经反射障碍伴随危险的血压升高、导致皮肤破裂的大小便失禁，以及频繁的尿路感染。失去对膀胱的控制也有深远的社会影响，导致生活质量下降，以及程序、用品和药物带来的巨额直接医疗成本。这项研究的长期目标是开发一种神经假体，以恢复神经疾病患者的膀胱功能(控制和排尿)，特别是脊髓损伤。我们正在寻求一种创新的方法，使用电刺激阴部神经(及其分支)中的传入(感觉)纤维，该纤维参与脊髓反射，要么抑制膀胱保持可控，要么激活膀胱产生排尿。这种新的方法与以往使用电刺激脊神经根的方法有很大的不同，因为它不需要脊椎椎板切除，不需要不可逆转的手术横断骶骨感觉神经根，并且刺激系统的传入而不是传出侧。在第一个资助期，我们开发和评估了一种闭环控制系统，以改善动物和脊髓损伤患者的可控性，我们发现并量化了对阴部传入刺激反应激活膀胱的反射的特性，我们确定了手术进入阴部N的途径，神经可以接受袖带植入，我们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。本提案的总体目标是通过电刺激阴部传入来提高膀胱排空的效率。在前一阶段，我们发现并表征了两种反射，当电刺激阴部传入时，这两种反射兴奋膀胱，抑制括约肌，并产生排尿。然而，所实现的排尿是有限的，在慢性脊髓损伤患者中，阴部传入神经的激活产生了小幅度或一过性的膀胱收缩。因此，我们将通过动物模型和脊髓损伤患者的互补性实验，开发和评估几种新的方法来增强阴部传入刺激诱导的膀胱排空。该项目的成功完成将推动开发一种有效的神经假体系统来恢复膀胱功能。

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.