Effects of activity dependent plasticity on recovery of bladder and sexual function after human spinal cord injury

活动依赖性可塑性对人脊髓损伤后膀胱和性功能恢复的影响

• 批准号: 9093814
• 负责人: SUSAN J HARKEMA
• 金额: $ 30.81万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-23 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9093814
• 关键词: Affect; Animals; Ataxia; Awareness; Biological Markers; Biological Neural Networks; Biopsy; Bladder; Bladder Dysfunction; Bladder Tissue; Body Weight; Brain-Derived Neurotrophic Factor; Caring; Case Study; Catheterization; Chemicals; Clinical; Contusions; Country; Data; Disease; Ejaculation; Electric Stimulation; Esthesia; Evaluation; Exercise; Female; Fertility; Flexor; Foundations; Frequencies; Genitourinary system; Hardness; Health; Hospitalization; Human; Hyperreflexia; Impairment; Individual; Infection; Injury; International; Intervention; Interview; Knowledge; Lead; Learning; Life; Locomotion; Locomotor training; Lower Extremity; Manuals; Mediating; Morbidity - disease rate; Motor; Motor Neurons; Operative Surgical Procedures; Oral; Outcome Measure; Paralysed; Paraplegia; Patient Self-Report; Patients; Penile Erection; Pharmaceutical Preparations; Quality of life; Questionnaires; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Reporting; Research Personnel; Residual volume; Rest; Risk; Seminal fluid; Sensory; Sex Functioning; Sexual Dysfunction; Source; Sphincter; Spinal; Spinal Cord; Spinal cord injury; Stents; Step training; System; Testing; Therapeutic; Tissues; Training; Translations; United States; Urethra; Urination; Urine; Urodynamics; Urologic Diseases; Viagra; Walking; Weight-Bearing state; arm; base; improved; improved functioning; indexing; inhibitor/antagonist; innovation; life time cost; male; neurotrophic factor; novel; phosphodiesterase V; pressure; prevent; response; satisfaction; symptom treatment; treadmill; urologic

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) results in impairments of locomotor, sensory and autonomic functions, severely affecting overall health and quality of life. Recent discoveries related to activity-dependent plasticity in humans have led to a widely implemented rehabilitation intervention, Locomotor Training, which includes stepping using body weight support on a treadmill with manual facilitation. Evidence suggests that this particular type of task specific training optimizes the lumbosacral spinal circuitry. We have intriguing evidence from four SCI individuals who are unable to stand or walk showing improved bladder and sexual function after undergoing Locomotor Training. These changes in urogenital function may be due to activity-dependent plasticity of lumbosacral circuitry that mediates micturition and erectile functions. Proper bladder management post-SCI is necessary to decrease the risk of upper urinary tract disease, a major source of morbidity. The life-long urologic care is required for SCI individuals, yet most efforts treat symptoms but do not improve intrinsic function. In addition, paraplegics rank sexual function as the function post-injury that should be given the highest priority in order to enhance quality of life. This proposal focuses on the mechanisms involved in the reorganization of spinal cord circuits for bladder and sexual function in response to activity-dependent plasticity induced by step training after SCI, with and without epidural stimulation. Stand training and/or arm crank exercise serve as controls. Of potential mechanistic importance is that neurotrophins have been implicated in modulating bladder function. It is therefore hypothesized that weight bearing task specific training for locomotion post-SCI induces plasticity of neural networks that mediate not just walking but bladder and sexual function as well and may do so for bladder function by reducing specific neurotrophins that are elevated post-SCI. Our unique approach will utilize the expertise of each investigator to 1) To determine whether the effect of weight-bearing task-specific training for locomotion on voiding frequency and urodynamic parameters is due to an interaction between locomotor and urinary bladder circuitry after traumatic incomplete upper motor neuron SCI in humans (versus standing or general exercise); 2) To assess the effect of LT on urine (biomarkers) and bladder (biopsy tissue) NGF and BDNF levels after severe incomplete SCI; 3) To determine the effect of weight-bearing task-specific training for locomotion on erectile function and sexual satisfaction after traumatic incomplete upper motor neuron SCI in humans; and 4) To assess the effect of epidural stimulation in combination with LT on voiding frequency, urodynamic parameters, erectile function, and bladder/urine NGF and BDNF levels after complete and motor complete/sensory incomplete upper motor neuron SCI in humans. Our innovative multi-disciplinary study may lead to the translation of a combination approach of weight bearing step training, epidural stimulation, and neurotrophic factor manipulation to promote functional recovery for multiple systems following SCI.

描述（由申请人提供）：脊髓损伤（SCI）导致运动，感觉和自主功能的障碍，严重影响整体健康和生活质量。与人类活动依赖性可塑性有关的最新发现导致了广泛实施的康复干预措施，运动训练，其中包括在手动促进的跑步机上使用体重支撑进行步进。证据表明这种特殊类型 特定于任务的训练优化了腰椎脊柱回路。在接受运动训练后，我们有四个无法站立或走路表现出改善的膀胱和性功能的SCI人的有趣证据。泌尿生殖功能的这些变化可能是由于倾向和勃起功能的腰s骨回路的活性依赖性可塑性所致。 SCI之后的适当膀胱管理对于降低上泌尿道疾病的风险是必要的，这是发病率的主要来源。 Sci需要终身泌尿科护理 个人，但大多数努力都会治疗症状，但不能改善内在功能。此外，截瘫患者将性功能列为伤害后的功能，应将其作为最高优先级，以提高生活质量。该提案的重点是脊髓回路重组膀胱和性功能的机制，以响应SCI后的阶跃训练引起的活动依赖性可塑性，并具有和没有硬膜外刺激。站立训练和/或手臂曲柄运动可作为控件。潜在的机理重要性是神经营养蛋白与调节膀胱功能有关。因此，假设体重轴承任务特定于SCI的运动特定训练会诱导神经网络的可塑性，这些神经网络不仅介导行走，而且还介导了膀胱和性功能，并且可以通过降低升高后SCI的特定特定的神经营养蛋白来促进膀胱功能。 我们的独特方法将利用每个研究者的专业知识1）确定是否承担运动频率对运动频率和尿动力学参数的影响是否是由于移动器和膀胱不完整的上部电动机之间的相互作用引起的人类中的神经元SCI（与站立或一般运动）； 2）评估LT对严重不完全SCI后LT的影响（生物标志物）和膀胱（活检组织）NGF和BDNF水平； 3）确定人类创伤不完整的上运动神经元SCI后，体重特定的任务训练对勃起功能和性满足的影响；和4）在完整且运动完整/感觉不完整的上运动不完全运动神经元SCI之后，评估硬膜外刺激与LT与LT结合的影响对空隙频率，尿动力学参数，勃起/尿液NGF和BDNF水平的影响。我们创新的多学科研究可能会导致体重轴承步骤训练，硬膜外刺激，硬膜外刺激的组合方法的翻译 和神经营养因子操纵以促进SCI后多个系统的功能恢复。