Interactions between Urological and Locomotor Systems during Treadmill Training i

跑步机训练期间泌尿系统和运动系统之间的相互作用 i

• 批准号: 8059127
• 负责人: Patricia J Ward
• 金额: $ 2.76万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-04 至 2014-01-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8059127
• 关键词: Adverse effects; Affect; Afferent Neurons; Animal Model; Animals; Behavioral; Bladder; Bladder Control; Bladder Dysfunction; Body Size; Body Weight; C Fiber; Capsaicin; Caring; Catheterization; Catheters; Chemicals; Clinical; Conscious; Contusions; Cystitis; Data; Development; Devices; Electromyography; Equilibrium; Exclusion Criteria; Exercise; Exhibits; Family; Forelimb; Functional disorder; Funding; Goals; Growth Factor; Health; Hindlimb; Implant; Infective cystitis; Inflammation; Inflammatory; Injury; Investigation; Knowledge; Lead; Learning; Life; Limb structure; Literature; Lower urinary tract; Maintenance; Manuals; Masks; Measures; Mediating; Messenger RNA; Metabolic; Methods; Molecular; Monitor; Morphology; Muscle; Operative Surgical Procedures; Organ; Outcome; Output; Paraplegia; Patient observation; Patients; Pattern; Performance; Pharmaceutical Preparations; Physical therapy exercises; Play; Polyuria; Quadriplegia; Quality of life; Rattus; Recovery; Recovery of Function; Reflex action; Regulation; Reporting; Respondent; Role; Saline; Self Perception; Sensory; Skeletal Muscle; Source; Sphincter; Spinal; Spinal Cord; Spinal cord injury; Spinal cord injury patients; Step training; Stimulus; Structure; Surveys; System; Testing; Therapeutic; Training; Upper Motor Neuron Disease; Urethral sphincter; Urodynamics; Viscera; Visceral; Walking; Water; arm; base; clinically relevant; cost; desensitization; design; effective therapy; irritation; male; neuronal cell body; neurotrophic factor; patient population; prevent; response; success; tibialis anterior muscle; urinary; urologic

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) results in detrimental effects on the upper and lower urinary tract. Currently there is no effective therapy for urological dysfunction. Having control over voiding function is of primary importance to this patient population as this affects independence, overall health, and self-image. Current attempts at treatments with various drugs and surgeries have unwanted side effects and limited success. One of our goals is to provide a natural therapeutic alternative. Body weight supported treadmill training is advancing our knowledge on how the spinal cord can learn and adapt, and the results of its positive effects for SCI patients continues to grow. We have clinical observations from patients that step training can have beneficial outcomes on bladder maintenance and that there is an inhibitory interaction between the limbs and the bladder. Therefore, we propose to study these observations in a clinically relevant animal model to identify mechanisms involved. Eighty-six male rats will receive a 225 kdyn force contusion injury at the T8 spinal level using the IH impact or device. Twenty-six rats will be implanted with a bladder catheter and EMG wires in the soleus and tibialis anterior muscles to determine the influence of noxious and innocuous bladder afferent input on locomotor (vesico-somatic) performance in intact, SCI, and inflammatory conditions. The role of C-fiber inputs will also be determined via capsaicin pre-treatment. Inflammation and distention from bladder may be altering sensory inputs for the lumbosacral cord, in turn altering the ability for locomotor output and spinal learning. Beginning 14 days post-injury, twenty rats will undergo daily step training on a treadmill with manual assistance for 8 weeks. Two other groups forelimb trained (n=20) and non-trained (n=20) will be tested simultaneously. Functional urological data will be obtained with 1) conscious cystometry- catheter infused saline and 2) natural voiding patterns gathered using a metabolic monitoring system. Terminal molecular studies eleven weeks post- SCI will assess the exercise's regulation of bladder mRNA content of various neurotrophic factors, which have been identified as important modulators in both the exercise and bladder dysfunction literature. Thus, this study will be the first to investigate the influence of exercise therapy on the spinally mediated reflexive relationship between viscera and somatic structures involving detrusor, external urethral sphincter, and limb musculature. Although partially masked in normal subjects, these reflexes are highly apparent after an upper motor neuron disease or SCI. Each part of this study is specifically designed to be applicable to the SCI patient and activity based therapies such as locomotor training. PUBLIC HEALTH RELEVANCE: Both quadriplegics and paraplegics rank bladder function as one of the most important factors affecting their quality of life, and 96.5% of 681 survey respondents believe that exercise is an important part of functional recovery yet at least 63.6% do not have access to a trained therapist to oversee their regiments. With over 1 million people in the U.S. alone affected by SCI and the annual cost in federal funds estimated at $9.7 billion, the knowledge gained from our study on locomotor training effects on bladder function will not only be immediately applicable to patients, providing immense improvements in quality of life, but also reduce life-long burdens on patient, family, and care centers.

描述（由申请人提供）：脊髓损伤（SCI）会对上尿路和下尿路产生不利影响。目前尚无有效的治疗泌尿系统功能障碍的方法。控制排尿功能对这一患者群体至关重要，因为这会影响独立性、整体健康和自我形象。目前尝试用各种药物和手术治疗有不必要的副作用和有限的成功。我们的目标之一是提供一种天然的治疗选择。体重支持的跑步机训练正在推进我们对脊髓如何学习和适应的知识，其对SCI患者的积极影响的结果继续增长。我们从患者的临床观察中发现，台阶训练可以对膀胱维持产生有益的结果，并且肢体和膀胱之间存在抑制性相互作用。因此，我们建议在临床相关的动物模型中研究这些观察结果，以确定相关的机制。86只雄性大鼠将使用IH冲击或装置在T8脊柱水平接受225 kdyn力的挫伤。将在26只大鼠的比目鱼肌和胫骨前肌中植入膀胱导管和EMG电线，以确定在完整、SCI和炎症条件下有害和无害的膀胱传入输入对运动（膀胱-躯体）性能的影响。C-纤维输入的作用也将通过辣椒素预处理来确定。膀胱的炎症和扩张可能改变腰骶髓的感觉输入，进而改变运动输出和脊髓学习的能力。从损伤后14天开始，20只大鼠将在跑步机上进行每天的台阶训练，并进行人工辅助，持续8周。另外两组前肢训练组（n=20）和未训练组（n=20）将同时进行测试。将通过1）清醒膀胱测压-导管输注生理盐水和2）使用代谢监测系统收集的自然排尿模式获得功能性泌尿学数据。SCI后11周的终末分子研究将评估各种神经营养因子的膀胱mRNA含量的运动调节，这些神经营养因子在运动和膀胱功能障碍文献中都被鉴定为重要的调节剂。因此，这项研究将是第一个调查的影响，运动疗法对脊髓介导的反射关系的内脏和躯体结构，包括逼尿肌，尿道外括约肌，四肢肌肉组织。虽然在正常受试者中部分被掩盖，但这些反射在上运动神经元疾病或SCI后非常明显。本研究的每个部分都是专门设计的，适用于SCI患者和基于活动的治疗，如运动训练。 公共卫生关系：四肢瘫痪和截瘫患者都将膀胱功能列为影响其生活质量的最重要因素之一，681名受访者中有96.5%认为运动是功能恢复的重要组成部分，但至少有63.6%的人无法获得训练有素的治疗师来监督他们的团队。仅在美国就有超过100万人受到SCI的影响，每年联邦基金的费用估计为97亿美元，我们从运动训练对膀胱功能影响的研究中获得的知识不仅可以立即应用于患者，大大改善生活质量，而且还可以减轻患者，家庭和护理中心的终身负担。