Bladder and Sphincter Control after Spinal Cord Injury

描述(由申请人提供)：在本次续期拨款申请中，基于我们先前资助的新发现，提出了一种恢复脊髓损伤(SCI)后排尿和控制功能的新方法。下尿路的正常功能是储存和及时排出尿液。这些功能在脊髓损伤后变得异常。逼尿肌和尿路括约肌在排尿过程中同时收缩(逼尿肌括约肌协同失调，DSD)，而逼尿肌在储存过程中也经常收缩(逼尿肌反射亢进，IH)。DSD可防止尿液完全排出，产生高膀胱压力，并需要每日导尿。从长远来看，高膀胱压力会导致膀胱输尿管反流和肾功能衰竭。膀胱中的残余尿液和导尿术会引起膀胱炎和感染。此外，尿失禁会导致膀胱储存量降低和膀胱内压力升高，从而导致大小便失禁、肾脏受损和膀胱肥大的风险。下尿路问题给脊髓损伤患者及其家属带来了巨大的医疗费用和巨大的社会心理影响。这个项目的目标是找到治疗DSD和DH的新方法。尽管在脊髓损伤后，电刺激能成功地恢复对膀胱的控制，但需要切断骶骨后根(背根切断术)以预防DSD和DH。背根切断术是破坏性的和不可逆转的，会导致反射性功能丧失和反射性排便。我们的新方法将利用脊髓损伤后剩余的和新出现的脊髓反射来恢复失去的功能，而不是通过背根切断术进一步破坏神经通路。在储尿期间，我们将电激活抑制阴部到膀胱的脊髓反射，以消除反射亢进的膀胱收缩，并治疗DH。当尝试排尿时，我们将激活兴奋性阴部到膀胱的脊髓反射以诱导膀胱收缩，同时电阻断阴部神经传导以松弛尿路外括约肌，从而治疗DSD。采用这种方法，可以获得较大的膀胱容量和最小残余尿量的低压排尿。我们的方法保留了肠道和性器官的脊髓反射功能，更重要的是为脊髓损伤患者提供了未来受益于神经再生和修复技术进步的机会。公共卫生相关性：脊髓损伤(SCI)后的泌尿系功能障碍导致巨大的医疗费用，并对脊髓损伤患者及其家人造成巨大的社会和心理影响。我们在这次拨款更新中提出的研究将找到新的方法来恢复脊髓损伤后的控制和排尿功能。我们的新方法还保留了肠道和性器官的脊髓反射功能，更重要的是为脊髓损伤患者提供了未来受益于神经再生和修复技术进步的机会。

DESCRIPTION (provided by applicant): In this renewal grant application, a novel approach to restore both micturition and continence functions after spinal cord injury (SCI) was proposed based on the new findings from our previous grant support. Normal functions of the lower urinary tract are storage and timely elimination of urine. These functions become abnormal after SCI. Detrusor and urethral sphincter contract simultaneously during voiding (detrusor sphincter dyssynergia, DSD) and the detrusor also contracts frequently during storage (detrusor hyperreflexia, DH). DSD prevents complete elimination of urine, generates high bladder pressure and requires daily urethral catheterization. High bladder pressure causes vesicoureteral reflux and renal failure in the long-term. Residual urine in the bladder and urethral catheterization cause cystitis and infection. In addition, DH causes a low bladder storage capacity and transient high intravesical pressures resulting in incontinence, risk for kidney damage and bladder hypertrophy. The problems of the lower urinary tract result in large medical cost and tremendous social and psychological impacts on people with SCI and their families. The goal of this project is to find new methods to treat both DSD and DH. Although electrical stimulation of sacral anterior roots has been successful to restore bladder control after SCI, it requires transection of sacral posterior roots (dorsal rhizotomy) to prevent DSD and DH. Dorsal rhizotomy is destructive and irreversible, and results in the loss of reflex sexual function and reflex defecation. Our new approach will utilize the remaining and newly emerged spinal reflexes after SCI to restore the lost functions, rather than further damaging the neural pathways by dorsal rhizotomy. During urine storage, we will electrically activate an inhibitory pudendal-to-bladder spinal reflex to abolish the hyperreflexic bladder contractions and treat DH. When voiding is attempted, we will activate an excitatory pudendal-to-bladder spinal reflex to induce bladder contraction while electrically blocking pudendal nerve conduction to relax the external urethral sphincter and thereby treat DSD. With this approach, a large bladder capacity and low pressure voiding with a minimal residual volume of urine will be expected. Our approach preserves the spinal reflex functions for bowel and sexual organ, and more importantly provides people with SCI the opportunity to benefit from advances in neural regeneration and repair techniques in the future. PUBLIC HEALTH RELEVANCE: The urological dysfunctions after spinal cord injury (SCI) result in large medical cost and tremendous social and psychological impacts on people with SCI and their families. Our studies proposed in this grant renewal will find new methods to restore both continence and micturition functions after SCI. Our new approach also preserves the spinal reflex functions for bowel and sexual organ, and more importantly provides people with SCI the opportunity to benefit from advances in neural regeneration and repair techniques in the future.